<SEC-DOCUMENT>0000874015-19-000068.txt : 20190509
<SEC-HEADER>0000874015-19-000068.hdr.sgml : 20190509
<ACCEPTANCE-DATETIME>20190509163741
ACCESSION NUMBER:		0000874015-19-000068
CONFORMED SUBMISSION TYPE:	10-Q
PUBLIC DOCUMENT COUNT:		60
CONFORMED PERIOD OF REPORT:	20190331
FILED AS OF DATE:		20190509
DATE AS OF CHANGE:		20190509

FILER:

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

	FILING VALUES:
		FORM TYPE:		10-Q
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		19811196

	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 3-31-2019
<TEXT>
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    <div style="text-align: center;"><font style="font-size: 18pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">SECURITIES AND EXCHANGE COMMISSION</font></div>
    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Washington, DC 20549</font></div>
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    <div style="text-align: center;"><font style="font-size: 18pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Form 10-Q</font></div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(Mark One)</font></div>
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                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934</font></div>
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    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">For the Quarterly Period Ended March 31, 2019</font></div>
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                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF SECURITIES EXCHANGE ACT OF 1934</font></div>
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    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">For the transition period from to</font></div>
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    <div style="text-align: center;"><font style="font-size: 18pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Ionis Pharmaceuticals, Inc.</font></div>
    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(Exact name of Registrant as specified in its charter)</font></div>
    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </font><br>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Delaware</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">33-0336973</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(State or other jurisdiction of<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><br>
                </font>incorporation or organization)</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(IRS Employer Identification No.)</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2855 Gazelle Court, Carlsbad, CA</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">92010</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(Address of Principal Executive Offices)</font></div>
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          <td style="width: 2%; vertical-align: bottom;">&#160;</td>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(Zip Code)</font></div>
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    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">760-931-9200</font></div>
    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(Registrant&#8217;s telephone number, including area code)</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Name of each exchange on which registered</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Trading symbol</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Common Stock, $.001 Par Value</font></div>
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          <td style="width: 2.54%; vertical-align: top;">&#160;</td>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The Nasdaq Stock Market, LLC</font></div>
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          <td style="width: 3.33%; vertical-align: top;">&#160;</td>
          <td style="width: 28.34%; vertical-align: top;">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8220;IONS&#8221;</font></div>
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    <div style="text-align: left; text-indent: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </font><br>
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    <div style="text-align: left; text-indent: 36pt; margin-bottom: 6pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Securities registered pursuant to Section 12(g) of the Act: <font style="font-size: 10pt; font-family:
          'Times New Roman', Times, serif; font-weight: bold;">None</font></font></div>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes <font style="font-size: 10pt; font-family: Wingdings;"></font> No <font style="font-size: 10pt; font-family: Wingdings;"></font></font></div>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any,
        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 and post such
        files). Yes <font style="font-size: 10pt; font-family: Wingdings;"></font> No<font style="font-size: 10pt; font-family: Wingdings;"></font></font></div>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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. (Check one):</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Large accelerated filer <font style="font-size: 10pt; font-family: Wingdings;"></font></font></div>
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          <td style="width: 50%; vertical-align: top;">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accelerated filer <font style="font-size: 10pt; font-family: Wingdings;"></font></font></div>
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          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
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          <td style="width: 50%; vertical-align: top;">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-accelerated filer <font style="font-size: 10pt; font-family: Wingdings;"></font></font></div>
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          <td style="width: 50%; vertical-align: top;">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Smaller reporting company <font style="font-size: 10pt; font-family: Wingdings;"></font></font></div>
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          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td style="width: 50%; vertical-align: top;">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Emerging growth company <font style="font-size: 10pt; font-family: Wingdings;"></font></font></div>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition
        period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. <font style="font-size: 10pt; font-family: Wingdings;"></font></font></div>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 <font style="font-size: 10pt; font-family: Wingdings;"></font> No <font style="font-size: 10pt; font-family: Wingdings;"></font></font></div>
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    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The number of shares of voting common stock outstanding as of May 2, 2019 was 140,322,994.</font></div>
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    <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">FORM 10-Q</font></div>
    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">INDEX</font></div>
    <div><br>
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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">PART I</font></div>
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          <td style="width: 83.07%; vertical-align: top;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">FINANCIAL INFORMATION</font></div>
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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ITEM 1:</font></div>
          </td>
          <td style="width: 83.07%; vertical-align: top;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Financial Statements:</font></div>
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          <td style="width: 83.07%; vertical-align: top;">&#160;</td>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; margin-left: 14.85pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Condensed Consolidated Balance Sheets as of March 31, 2019 (unaudited) and December 31, 2018</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3</font></div>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; margin-left: 14.85pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Condensed Consolidated Statements of Operations for the three months ended March 31, 2019 and 2018 (unaudited)</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">4</font></div>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; margin-left: 14.85pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Condensed Consolidated Statements of Comprehensive Income (Loss) for the three months ended March 31, 2019 and
                2018 (unaudited)</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">5</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
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            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6</font></div>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; margin-left: 14.85pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Condensed Consolidated Statements of Cash Flows for the three months ended March 31, 2019 and 2018 (unaudited)</font></div>
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            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">7</font></div>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; margin-left: 14.85pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to Condensed Consolidated Financial Statements (unaudited)</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8</font></div>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ITEM 2:</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations:</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; margin-left: 14.85pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Overview</font></div>
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            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">25</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; margin-left: 14.85pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Results of Operations</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">27</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; margin-left: 14.85pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Liquidity and Capital Resources</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">33</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ITEM 3:</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Quantitative and Qualitative Disclosures about Market Risk</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">34</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ITEM 4:</font></div>
          </td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Controls and Procedures</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">35</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">PART II</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">OTHER INFORMATION</font></div>
          </td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">35</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ITEM 1:</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Legal Proceedings</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">35</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">
            <div>&#160;</div>
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ITEM 1A:</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">
            <div>&#160;</div>
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Risk Factors</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">35</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>&#160;</div>
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ITEM 2:</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>&#160;</div>
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Unregistered Sales of Equity Securities and Use of Proceeds</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255); text-align: right;">44<br>
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        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ITEM 3:</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Default upon Senior Securities</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255); text-align: right;">44<br>
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        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ITEM 4:</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Mine Safety Disclosures</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">39</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ITEM 5:</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Other Information</font></div>
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          <td style="width: 8%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">44</font></div>
          </td>
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        <tr>
          <td style="width: 8.93%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 8%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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          <td style="width: 8.93%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ITEM 6:</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Exhibits</font></div>
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            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">44</font></div>
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          <td style="width: 83.07%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>
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        TEGSEDI (inotersen) and WAYLIVRA (volanesorsen), are the property of Akcea Therapeutics,&#160;Inc. 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.</font></div>
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          <td valign="bottom" nowrap="nowrap" 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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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>
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          <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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Contracts receivable</font></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>
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          <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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12,759</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; 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>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">98,686</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">102,473</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">132,160</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Patents, net</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">25,220</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">24,032</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Long-term deferred tax assets</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">277,247</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">290,796</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Deposits and other assets</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">25,954</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12,910</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total assets</font></div>
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          <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">
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,835,889</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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">
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,667,784</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Current liabilities:</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accounts payable</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accrued liabilities</font></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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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Income taxes payable</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1 percent convertible senior notes</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">577,415</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Long-term obligations, less current portion</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">16,305</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">4,914</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Long-term mortgage debt</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">59,860</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">59,842</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; 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: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">140</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">138</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additional paid-in capital</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,117,969</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,047,250</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accumulated other comprehensive loss</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(32,016</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; 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>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(882,850</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(967,293</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;&#160;&#160;Noncontrolling interest in Akcea Therapeutics, Inc.</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">179,769</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">139,081</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total stockholders&#8217; equity</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,387,420</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,187,160</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,835,889</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,667,784</font></div>
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    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">See accompanying notes.</font></div>
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  <div id="TRGRSegment:50bdda75-988b-44d6-9bbd-c3fb76083d5b">
    <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS</font></div>
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          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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;" colspan="6">
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          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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;" colspan="2">
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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: -27pt; margin-left: 45pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA royalties</font></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">
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">59,711</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -27pt; margin-left: 45pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Licensing and other royalty revenue</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,623</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">942</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 45pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total commercial revenue</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">68,088</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">42,023</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; 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>
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          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">43,653</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; 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: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">147,720</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Investment income</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12,142</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3,610</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Interest expense</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Other expenses</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(147</font></div>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></div>
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          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net income (loss)</font></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>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net (income) loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</font></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>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">9,392</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; 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: 76%; background-color: #FFFFFF;">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">84,443</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,420</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Basic net income (loss) per share</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.63</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(0.01</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Shares used in computing basic net income (loss) per share</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">138,582</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">125,330</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Diluted net income (loss) per share</font></div>
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          <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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.62</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(0.01</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Shares used in computing diluted net income (loss) per share</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">141,537</font></div>
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    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">See accompanying notes.</font></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="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">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Comprehensive income (loss)</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" 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: 76%; background-color: #FFFFFF;">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Comprehensive (income) loss attributable to noncontrolling interests</font></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>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(9,399</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Comprehensive income (loss) attributable to Ionis Pharmaceuticals, Inc. stockholders</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">88,850</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(2,888</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
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    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">See accompanying notes.</font></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" nowrap="nowrap" 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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          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Noncontrolling</font></div>
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          <td valign="bottom" nowrap="nowrap" 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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          <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
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          <td valign="bottom" nowrap="nowrap" 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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          <td valign="bottom" nowrap="nowrap" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Capital</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Loss</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Equity</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Therapeutics, Inc.</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Equity</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
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            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Balance at December 31, 2017</font></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: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">124,976</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">125</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,553,681</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(31,759</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,241,034</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">281,013</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">84,267</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">365,280</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net loss</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,420</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,420</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,420</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Change in unrealized gains (losses), net of tax</font></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: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,530</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,530</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Balance at March 31, 2018</font></div>
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          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">125,449</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">125</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,576,954</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(33,234</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,242,454</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">301,391</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 20%; 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: 7%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Balance at December 31, 2018</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">137,929</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">138</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,047,250</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(32,016</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(967,293</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,048,079</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">139,081</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,187,160</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net income</font></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: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">84,443</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">84,443</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">84,443</font></div>
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          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></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>
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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>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">67,057</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">67,059</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">67,059</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Stock-based compensation expense</font></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>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">45,505</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">45,505</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(130</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">140</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(27,608</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(882,850</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,207,651</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,387,420</font></div>
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    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">See accompanying notes.</font></div>
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    <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS</font></div>
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    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(Unaudited)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" 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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              <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
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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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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">
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">90,884</font></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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          <td valign="bottom" nowrap="nowrap" 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: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Depreciation</font></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>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Amortization of patents</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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" nowrap="nowrap" 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">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,192</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Amortization of debt issuance costs</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">474</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">441</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,726</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">26,097</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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" nowrap="nowrap" 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">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">922</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,802</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">11,422</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accounts payable</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(17,191</font></div>
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          <td valign="bottom" nowrap="nowrap" 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">&#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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accrued compensation</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <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>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; 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>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(91,157</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Proceeds from the sale of short-term investments</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">426,868</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">173,724</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Purchases of property, plant and equipment</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(3,229</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(2,343</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: rgb(204, 238, 255); padding-bottom: 2px;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Acquisition of licenses and other assets, net</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,032</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(738</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 54pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net cash provided by (used in) investing activities</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(70,174</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">79,486</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Financing activities:</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Proceeds from equity awards</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">67,057</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">5,675</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: 17.85pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Payments of tax withholdings related to vesting of employee stock awards</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(7,597</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 54pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net cash provided by financing activities</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">5,224</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net increase in cash and cash equivalents</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">97,875</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Cash and cash equivalents at beginning of period</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">278,820</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">129,630</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; 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: 76%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Cash and cash equivalents at end of period</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" 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: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">375,811</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" 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: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">227,505</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Supplemental disclosures of cash flow information:</font></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">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Interest paid</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">667</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">644</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Supplemental disclosures of non-cash investing and financing activities:</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Right-of-use assets obtained in exchange for lease liabilities</font></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">
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">13,557</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Amounts accrued for capital and patent expenditures</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,864</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,091</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

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    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">See accompanying notes.</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><br>
    </div>
  </div>
  <div id="TRGRSegment:b246f81c-4208-416d-a473-7785cf25fd39">
    <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">NOTES TO CONDENSED CONSOLIDATED FINANCIAL STATEMENTS</font></div>
    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31, 2019</font></div>
    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(Unaudited)</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:f805fb02-4717-455f-b724-d5f8acab4cc4">
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.&#160; Basis of Presentation</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:b5d004e0-77b9-432f-bf38-d0495b9e8cd5">
    <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 months ended March 31, 2019 and 2018 on the
      same basis as the audited financial statements for the year ended December 31, 2018. 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. Results for the interim periods are not necessarily indicative of the results 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, 2018 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:77f9936b-92e6-432c-b10f-8cc58dcdf274">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the condensed consolidated financial statements, we
        included the accounts of Ionis Pharmaceuticals,&#160;Inc. and the consolidated results of our majority owned affiliate,&#160;Akcea Therapeutics, Inc. and its wholly owned subsidiaries. We formed Akcea in December 2014. </font>In July 2017, Akcea completed
      an <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">initial public offering, or IPO,</font> and therefore, beginning in July 2017, we no longer owned 100 percent of Akcea. In the first quarter of 2019, we received 2.8
      million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>, increasing our ownership to approximately 76 percent at March 31, 2019. We reflected the increase in our
      ownership in these financial statements. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Refer to the section titled &#8220;Noncontrolling Interest in Akcea&#8221; in Note 2, </font><font style="font-size: 10pt; font-family: 'Times
        New Roman', Times, serif; font-style: italic;">Significant Accounting Policies,</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for further information related to our accounting for our investment in Akcea.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:23544735-6037-4320-8b21-89e209b88342">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unless the context requires otherwise, &#8220;Ionis&#8221;, &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221; refers to Ionis Pharmaceuticals, Inc. and its majority
      owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries.</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:e29f371d-c746-4493-89a1-64e89e3031db">
    <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2.&#160; Significant Accounting Policies</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:f8ad7104-6f64-4900-aeb5-87c990df353d">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><font style="background-color: #FFFFFF;">Revenue Recognition</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Our Revenue Sources</u></font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting
        the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing
        revenue, we include the amounts in deferred revenue on our consolidated balance sheet.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We will also recognize as
        commercial revenue future sales milestone payments and royalties we earn under our partnerships.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Commercial Revenue: TEGSEDI Product Sales, net</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We added product sales from TEGSEDI to our
          commercial revenue in the fourth quarter of 2018. </font>In the U.S., TEGSEDI is distributed through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in
        the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients. In Germany, TEGSEDI is distributed
        through a non-exclusive distribution model with a 3PL that takes title to TEGSEDI. The 3PL is our sole customer in Germany. The 3PL in Germany then distributes TEGSEDI to hospitals and pharmacies.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Research and development revenue under collaborative agreements</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We often 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We provide details about our collaboration agreements in Note 7, <font style="font-size: 10pt; font-family: 'Times New
          Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements,</font> in our Annual Report on Form 10-K for the year ended December 31, 2018<font style="font-size: 10pt; font-family: 'Times New Roman', Times,
          serif; font-style: italic;">.</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</font>Under each collaboration note we discuss our specific revenue recognition conclusions, including our
        significant performance obligations under each collaboration.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Steps to Recognize Revenue</u></font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The
        five step process is as follows:</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">8</font></div>
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    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z61bd48488b8040a4a1400213a97c1489" class="DSPFListTable">

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              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">1.</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Identify the contract</font></div>
              </td>
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    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met
        each of the following criteria:</font></div>
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    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z9a37bd3a43a1444a9cac1a58ad35016c" class="DSPFListTable">

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              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We and our partner approved the contract and we are both committed to perform our obligations;</font></div>
              </td>
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    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z0a67c3d9b65b4fffa6a24335490271f6" class="DSPFListTable">

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              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have identified our rights, our partner&#8217;s rights and the payment terms;</font></div>
              </td>
            </tr>

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    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zccf7fc7223244b86bdc5e95e2b2ea9e4" class="DSPFListTable">

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              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a
                    result of the contract; and</font></div>
              </td>
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        </table>
      </div>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z44893922250d420aa64f1686826f0e05" class="DSPFListTable">

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              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We believe collectability is probable.</font></div>
              </td>
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      </div>
    </div>
    <div style="margin-bottom: 10pt;"><br>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z92a0f39dba144032a5f29838b38475d7" class="DSPFListTable">

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

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We next identify the distinct goods and services we are required to provide under the contract. Accounting rules refer to
        these as our performance obligations. We typically have only one performance obligation at the inception of a contract, which is to perform R&amp;D services.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Often times we enter into a collaboration agreement in which we provide our partner with an option to license a medicine
        in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the
        inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide
        additional goods and services as requested by our partner are not material rights. These items are contingent upon future events that may not occur. When a partner exercises its option to license a medicine or requests additional goods or services,
        then we identify a new performance obligation for that item.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the
        license and we do not have any additional performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
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              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">3.</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Determine the transaction price</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the
        collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone
        payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because
        the payments are not probable and are contingent on certain events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most
        likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone
        payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the
        majority of our milestone payments are contingent upon events that are not within our control and are usually based on scientific progress. For example, in the first quarter of 2019, we earned $35 million in milestone payments from Roche when it
        dosed the first patient in the Phase 3 study of IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx </sub>(RG6042) <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">because we do not have any performance obligations related to these milestone payments as
          Roche is conducting the Phase 3 study of IONIS-HTT</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</font> At December 31, 2018, we determined it was not probable that we could earn these milestone
        payments.&#160;As such, we did not recognize any revenue associated with the milestone payments in 2018.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zf5256de43a5c4521be6fe565e81e2df1" class="DSPFListTable">

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

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction
        price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the
        transaction price to each performance obligation based on the relative stand-alone selling price.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price
        for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the
        amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z5a9909f3565540c3adab71a7838f31e7" class="DSPFListTable">

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              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Estimated future product sales;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zb3075271c8004df78d4cb2ad890a6c8c" class="DSPFListTable">

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              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Estimated royalties on future product sales;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z03bad5cfe82e42158873d8e9a1970c9c" class="DSPFListTable">

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              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Contractual milestone payments;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z13dc18dc542a42e09de2e4812f6933b4" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Expenses we expect to incur;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z804f3358f6de4bbf8321eab00c2a1d29" class="DSPFListTable">

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              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Income taxes; and</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="za5acc9719c1d4603a96899c0a3257aa2" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">A discount rate.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">9</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
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    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the
        specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z0524b6735f374524acfafb9ab3a467b5" class="DSPFListTable">

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              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The number of internal hours we estimate we will spend performing these services;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="za479830ea4b14b60b4fc503d0a809e02" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The estimated cost of work we will perform;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z20c053b67f794f2eb89aa23338e18eef" class="DSPFListTable">

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

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="ze0c6a2fd8bf84214a9c2e452e868c81c" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The estimated cost of API we will use.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver,
        accounting guidance requires us to include a markup for a reasonable profit margin.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone
        selling prices.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z3436fc9c7cc04205a1c6cf83ae13b310" class="DSPFListTable">

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              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">5.</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Recognize revenue</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are
        executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use
        of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use
        are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a
        given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach
        requires us to make numerous estimates and use significant judgement. If our estimates or judgements <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">change over the course of the collaboration, they may affect the
          timing and amount of revenue that we recognize in the current and future periods.</font></font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Commercial Revenue:
            SPINRAZA royalties and Licensing and other royalty revenue</u></font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize royalty revenue in the period in
          which the counterparty sells the related product, which in certain cases may require us to estimate our royalty revenue. </font>We recognize royalties from SPINRAZA sales in the period Biogen records the sale of SPINRAZA.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Commercial Revenue:
            TEGSEDI Product Sales, net</u></font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize TEGSEDI product sales in the
          period </font>when our customer obtains control of TEGSEDI, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and
        priced at fair value as selling, general and administrative expenses in our condensed consolidated statements of operations. Otherwise payments to customers or other parties in the distribution channel that do not meet those criteria are classified
        as a reduction of revenue, as discussed further below. We exclude from revenues, taxes collected from customers relating to product sales and remitted to governmental authorities.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Reserves for TEGSEDI Product Sales</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We record TEGSEDI product sales at our net sales price, or transaction price. We include in our transaction price
        estimated reserves for discounts, returns, chargebacks, rebates, co-pay assistance and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our
        reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as reductions of accounts receivable when the amount is payable to our customer or a current liability when the amount is payable to a
        party other than our customer in our condensed consolidated balance sheet. In certain cases, our estimates include a range of possible outcomes that are probability-weighted for relevant factors such as our historical experience, current
        contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When
        calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The
        actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net TEGSEDI product sales in the respective period.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following are the components of variable consideration related to TEGSEDI product sales:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Chargebacks: </font>In
        the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer
        charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We record reserves for these chargebacks related to TEGSEDI product sales to our U.S. customer during the reporting
        period. We also estimate the amount of product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">10</font></div>
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    </div>
    <div><br>
    </div>
    <div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Government rebates</font>:
        We are subject to discount obligations under government programs, including Medicaid programs and Medicare in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid
        and Medicare rebates based on a range of possible outcomes that are probability-weighted for the estimated payer mix. We record these reserves as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing
        our TEGSEDI product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program.
        On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Trade discounts and
          allowances: </font>We provide customary invoice discounts on TEGSEDI product sales to our U.S. customer for prompt payment. We record this discount as a reduction of TEGSEDI product sales in the period in which we recognize the related product
        revenue. In addition, we receive and pay for various distribution services from our U.S. customer and wholesalers in our U.S. distribution channel. For services we receive that are either not distinct from the sale of TEGSEDI or for which we cannot
        reasonably estimate the fair value, we classify such fees as a reduction of TEGSEDI product sales.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Product Returns: </font>Our
        U.S. customer has return rights and the wholesalers have limited return rights primarily related to the TEGSEDI&#8217;s expiration date. We estimate the amount of TEGSEDI product sales that our customer may return. We record our return estimate as an
        accrued refund liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales, in the same period we recognize the related sale. Based on our distribution model for TEGSEDI, contractual
        inventory limits with our customer and wholesalers and the price of TEGSEDI, we believe we will have minimal returns. Our customer in Germany only takes title to the product once it receives an order from a hospital or pharmacy and therefore does
        not maintain any inventory of TEGSEDI, as such we do not estimate returns in Germany.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Other incentives: </font>In
        the U.S., we estimate reserves for other incentives including co-payment assistance we provide to patients with commercial insurance who have coverage and reside in states that allow co-payment assistance. We record a reserve for the amount we
        estimate we will pay for co-payment assistance. We base our reserve on the number of estimated claims and our estimate of the cost per claim related to TEGSEDI product sales that we have recognized as revenue. We record our other incentive reserve
        estimates as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales, in the same period we recognize the related sale.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Research and development
            revenue under collaboration agreements:</u></font></font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Upfront Payments</u></font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we enter into a collaboration agreement with an upfront payment, we typically record the entire upfront payment as
        deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. For example, under our <font style="font-size: 10pt;
          font-family: 'Times New Roman', Times, serif;">collaboration agreement with Roche to</font><font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;for the treatment of complement-mediated diseases</font>, we received a $75 million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our
        single performance obligation, R&amp;D services. We are amortizing the $75 million upfront payment using an input method over the estimated period of time we are providing R&amp;D services.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Milestone Payments</u></font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are required to include additional consideration in the transaction price when it is probable. We typically include
        milestone payments for R&amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because there is considerable uncertainty in the research and development processes that trigger
        these payments under our collaboration agreements. 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 we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For
        example, in the third quarter of 2017, we initiated a Phase 1/2a clinical study of IONIS-MAPT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx </sub>in patients with mild Alzheimer&#8217;s disease. We earned a $10 million milestone payment from Biogen related to the initiation of this study. We
        added this payment to the transaction price and allocated it to our R&amp;D services performance obligation. We are recognizing revenue from this milestone payment over our estimated period of performance.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner
        achieves the milestone event and we do not have a performance obligation. For example, in the first quarter of 2019, we recognized $35 million in milestone payments <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">when
          Roche dosed the first patient in a Phase 3 study for IONIS-HTT</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We concluded that the milestone payments were not related to our R&amp;D services
          performance obligation. Therefore, we recognized these milestone payments in full in the first quarter of 2019.</font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>License Fees</u></font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generally recognize as revenue the total
          amount we determine to be the stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the
          license after delivery. </font>For example, in the first quarter of 2019, we earned a $150 million license fee when Novartis licensed AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> from us.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">11</font></div>
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    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Amendments to Agreements</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items
        to determine the accounting for the amendment:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z2a2df50de8da47ab93f8ab12c55a9b95" class="DSPFListTable">

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

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z6aac75f36fa84ba2a2021fd5511b42e7" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2)</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If the goods and/or services are at a stand-alone selling price.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original
        agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and at their stand-alone selling price, we then assess whether the remaining goods or
        services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from
        the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated
        revenue as a cumulative adjustment.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, in May 2015, we entered into an
          exclusive license agreement with Bayer to develop and commercialize IONIS-FXI</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the prevention of thrombosis. As part of the agreement, Bayer paid
          us a $100 million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in people with
          end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times,
          serif;"> and to initiate development of IONIS-FXI-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $75 million. We are also
          eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and IONIS-FXI-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size:
          10pt; font-family: 'Times New Roman', Times, serif;">. Under the 2017 amendment, we concluded we had a new agreement with three performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, to provide R&amp;D services and to deliver API. We allocated the $75 million transaction price to these performance obligations. </font>Refer to <font style="font-size:
          10pt; font-family: 'Times New Roman', Times, serif;">Note 7, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</font>, for further
        discussion <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">of our accounting treatment for our Bayer collaboration.</font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Multiple Agreements</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such
        agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the
        agreements:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zb5e685204e53454ab921ba522f696b20" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Whether the agreements were negotiated together with a single objective;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z26d9dcd1f0584f51865718d8ed8ee728" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z1d74be74ef4f4eb1aa33ad2b177522fd" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Whether the goods and/or services promised under the agreements are a single performance obligation.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that
        accounting guidance requires us to account for them as a combined arrangement.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: a new
        strategic neurology collaboration agreement and a stock purchase agreement, or SPA. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We evaluated the Biogen agreements to determine whether we should treat the agreements
          separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a
          combined basis.</font></font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:8aa4a824-1d0c-463b-896a-b511fde1d100">
    <div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents
          the amounts we have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we
          consider the contract receivable to be unconditional. We typically receive payment within one quarter of billing our partner or customer</font>.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:81956029-ca4a-4712-a3b8-6e755a83e521">
    <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled SPINRAZA Royalties</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are
        eligible to bill Biogen for SPINRAZA royalties. We include these unbilled amounts in other current assets on our condensed consolidated balance sheet.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:702c1ef3-b0e7-42f4-a993-0a43d4ab3bdd">
    <div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers
          and receive payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue on our condensed consolidated balance sheet.</font> During
        the three months ended March 31, 2019 and 2018, we recognized $40.3 million and $34.9 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue
        recognition policy above.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:4498981f-4b16-4b2b-8c99-a4e3bd63b3db">
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">12</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
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    </div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Products Sold</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our cost of products sold includes manufacturing costs, transportation and freight costs and indirect overhead costs
        associated with the manufacturing and distribution of TEGSEDI. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of products sold. Prior to obtaining regulatory approval in July 2018, we
        expensed a significant portion of the costs we incurred to produce the TEGSEDI supply we are using in the commercial launch as research and development expense. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We
          previously recognized $0.3 million of costs to produce TEGSEDI related to the TEGSEDI commercial revenue we recognized in the</font> three months ended March 31, 2019.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:4c1c57ec-1101-402d-8469-50b1c183a740">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Prior to Akcea&#8217;s IPO in July 2017, we owned 100 percent of Akcea. From the closing of Akcea&#8217;s IPO in July 2017 through
        mid-April 2018, we owned approximately 68 percent<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font>of Akcea. In the second, third and fourth quarters of 2018, we received additional shares of Akcea&#8217;s stock related
        to our license of TEGSEDI and AKCEA-TTR-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> to Akcea, increasing our ownership percentage to approximately 75 percent. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee
        Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>, increasing our ownership to approximately 76 percent at March 31, 2019. We reflected this increase in our ownership percentage in these financial statements as an adjustment to
        noncontrolling interest. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The shares third parties own represent an interest in Akcea&#8217;s equity that is not controlled by us. However, as we continue to maintain overall
          control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our condensed consolidated financial statements. We reflect the noncontrolling interest attributable to other owners of Akcea&#8217;s
          common stock in a separate line on the statement of operations and a separate line within stockholders&#8217; equity in our condensed consolidated balance sheet. In addition, we record a noncontrolling interest adjustment to account for the stock
          options Akcea grants, which if exercised, will dilute our ownership in Akcea. This adjustment is a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based
          compensation expense Akcea had recognized.</font></font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:b5fbdc46-9b93-4e17-a78e-6bd68798b238">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, cash equivalents and investments</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents.
        Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the
        fiscal period for identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments. We use the
        specific identification method to determine the cost of securities sold.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies
        that we received as part of a technology license or partner agreement. At March 31, 2019, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity
        investments in four privately-held companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:5277ddff-9f2f-452b-bc69-bffdd0dffd0c">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventory valuation</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or market value under the
        first-in, first-out method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials they have alternative future uses. We include in inventory raw material costs
        for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw
        material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these
        costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency.</font></div>
    <div style="text-align: justify;"><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We obtained the first regulatory approval for TEGSEDI in July 2018. At March 31, 2019 and December 31, 2018, our physical
        inventory for TEGSEDI included API that we produced prior to when we obtained regulatory approval and accordingly has no cost basis as we had previously expensed the costs as R&amp;D expenses.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We review our inventory periodically and
          reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value,
          including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We did not record any inventory write-offs for the three months ended March 31, 2019 and 2018. Total inventory was $11.1 million
          and $8.6 million as of </font>March 31, 2019 and December 31, 2018<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively.</font></font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:8b5155d7-7c08-4a1e-b2c1-de63c5656b8d">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Leases</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Topic 842 Adoption</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In February 2016, the FASB issued amended accounting guidance related to lease accounting. This guidance supersedes the
        lease requirements we previously followed in Accounting Standards Codification, or ASC, Topic 840, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</font>, or Topic 840, and created a new
        lease accounting standard, Topic 842, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</font>, or Topic 842. Under Topic 842, an entity will record on its balance sheet all leases with a term
        longer than one year. Further, an entity will record a liability with a value equal to the present value of payments it will make over the life of the lease (lease liability) and an asset representing the underlying leased asset (right-of-use
        asset). The new accounting guidance requires entities to determine if its leases are operating or financing leases. Entities will recognize expense for operating leases on a straight-line basis as an operating expense. If an entity determines a
        lease is a financing&#160;lease, it will record</font></div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">13</font></div>
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    </div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. We adopted Topic 842 on
        January 1, 2019 and adjusted our opening balance sheet on that date for our right-of-use operating lease assets and operating lease liabilities. At adoption, we recorded $13.5 million in right-of-use operating lease assets and $18.5 million in
        operating lease liabilities, of which we classified $2 million as a current liability. We adopted Topic 842 using the available practical expedients<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> permitted under the
          transition guidance within the new standard, which among other things, allowed us to carry forward the historical lease classification of those leases we had in place as of January 1, 2019. </font>The adoption did not have an impact on our
        condensed consolidated statement of operations.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a
        right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed consolidated balance sheet for operating leases greater than one year. Our right-of-use assets represent our right to use an
        underlying asset for the lease term and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value
        of the future minimum lease payments we will pay over the lease term.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</font>We determined the lease term at the commencement date of the lease, and in
        certain cases our lease term could include renewal options if we concluded we were reasonably certain that we will exercise the renewal option.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">As our current leases do not provide an interest rate implicit in the lease, we used our or Akcea&#8217;s incremental borrowing
        rate, based on the information available on the date we adopted Topic 842 in determining the present value of future payments. Our right-of-use operating lease asset also includes any lease payments we made and excludes any tenant improvement
        allowances we received. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the
        expense.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:05fc2b94-61a4-4195-bc94-75d5c93b4dfa">
    <div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, development and patent expenses</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:1d6a6bef-e74e-4b9c-9dc5-27324e82a8ec">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing
      costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being
      rendered, we record those amounts as prepaid assets on our condensed consolidated balance sheet and we expense them as the services are provided.</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:a033fa75-aaf6-4a71-9441-5175da34dce7">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs
      over the useful life of the patent, beginning with the date the United States Patent and Trademark Office, or foreign equivalent, issues the patent. We review our capitalized patent costs regularly to ensure that they include costs for patents and
      patent applications that have future value. We evaluate patents and patent applications that we are not actively pursuing and write off any associated costs.</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:81e94cc1-3c99-4165-908a-8e917cf9a3c4">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets
        and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and
        research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and
        Jobs Act of 2017, or the Tax Act. The Tax Act created a new requirement on global intangible low-taxed income, or GILTI, earned by foreign subsidiaries for tax years beginning on or after January 1, 2018. The GILTI provisions require foreign
        subsidiary earnings in excess of an allowable return on the foreign subsidiary&#8217;s assets to be included in our U.S. income tax return. Under U.S. GAAP, we are permitted to make an accounting policy election to either treat taxes due on future
        inclusions in U.S. taxable income related to GILTI as a current-period expense when incurred or to factor such amounts into our measurement of deferred taxes. We have made the election to account for GILTI as a component of current taxes incurred
        rather than as a component of deferred taxes.</font></div>
    <div><br>
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  </div>
  <div id="TRGRSegment:32cdd276-6272-457c-8ae9-c3582bfabb54">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Long-lived assets</div>
    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We evaluate long-lived assets, which include property, plant and equipment, right-of-use operating lease assets and patent
        costs acquired from third parties, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.</font></div>
    <div><br>
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  <div id="TRGRSegment:34abc747-bcb9-447e-8827-bcf8e4cf9337">
    <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The preparation of condensed consolidated financial statements in conformity with accounting principles generally accepted
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    <div><br>
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  <div id="TRGRSegment:ab81a655-b4aa-442b-a8ba-313a1cffbfd9">
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">14</font></div>
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    <div><br>
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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;">Basic and diluted net income (loss) per share</div>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Basic net income (loss) per share</font></div>
    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The calculation of total net income (loss) attributable to our common stockholders for the three months ended March 31,
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  <div id="TRGRSegment:2578a751-1ba7-4925-a8c6-85d2e7a4aee0">
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three months ended March 31, 2019</font></div>
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          <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Weighted</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Average Shares</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea&#8217;s</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Per Share</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Ionis&#8217; Portion of</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea&#8217;s Net Loss</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: top;">&#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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Common shares</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">68,582</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.35</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">23,846</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea&#8217;s net income attributable to our ownership</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">23,846</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Ionis&#8217; stand-alone net income</font></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%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">63,697</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net income available to Ionis common stockholders</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">87,543</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Weighted average shares outstanding</font></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%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">138,582</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Basic net income per share</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.63</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:71426582-8b25-4586-95e3-185d51e2f7a6">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the three months ended <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">March
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    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z9d4566b898cd415b93c9266431415af0">

        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three months ended March 31, 2018</font></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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Weighted</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Average Shares</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Owned in Akcea</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea&#8217;s</font></div>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Per Share</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Ionis&#8217; Portion of</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea&#8217;s Net Loss</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: top;">&#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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Common shares</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">45,448</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(0.44</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(19,997</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea&#8217;s net loss attributable to our ownership</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(19,997</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
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        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Ionis&#8217; stand-alone net income</font></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%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">18,785</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net loss available to Ionis common stockholders</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,212</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Weighted average shares outstanding</font></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%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">125,330</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; 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: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Basic net loss per share</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(0.01</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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    </table>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:2113eb0d-5d21-495d-9b18-5ae011e7184b">
    <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Dilutive net income (loss per share)</div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For the three months ended March 31, 2019, we had net income available to Ionis common stockholders. As a result, we computed diluted net
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    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:5788a8d2-f3ea-42b1-9550-9bbbe8d32508">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our diluted net income per share for the three months ended March 31, 2019 as follows (in thousands except per share
      amounts):</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zebeb0b54813440f893ee6625ceaa62fa">

        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three months ended March 31, 2019</font></div>
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          <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Income</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(Numerator)</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Shares</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(Denominator)</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Per-Share</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Amount</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top;">&#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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net income available to Ionis common stockholders</font></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%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">87,543</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">138,582</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Shares issuable upon exercise of stock options</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Shares issuable upon restricted stock award issuance</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">665</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Shares issuable related to our ESPP</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">38</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Income available to Ionis common stockholders</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">87,543</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">141,537</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.62</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:98746993-3909-4b93-b0a6-3d32f6954f8d">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three months ended March 31, 2019, the calculation excluded the 1 percent notes because the effect on diluted earnings per share
      was anti-dilutive.</div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">15</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
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    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For the three months ended March 31, 2018, 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:</font></div>
    <div><br>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="za12e87d98d5b436ebf330460bff59546" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1 percent convertible senior notes;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zdd815d9480584dee9e1670d27dd5a848" class="DSPFListTable">

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

        </table>
      </div>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zdeb17a777a4342cc9367a57d4fc59283" class="DSPFListTable">

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

        </table>
      </div>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z9476d99719dc40ad929aca72d7149034" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Employee Stock Purchase Plan, or ESPP.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:c4f71491-3b33-4976-832e-205a2977d481">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible debt</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for convertible debt instruments that may be settled in cash upon conversion (including partial cash
        settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate. We determine the carrying amount of the liability component by measuring the fair value of similar
        debt instruments that do not have the conversion feature. If no similar debt instrument exists, we estimate fair value by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit
        standing, yield curves and volatilities. To determine the fair value of the debt component we are required to use accounting estimates and assumptions. These estimates and assumptions are judgmental in nature and could have a significant impact on
        the determination of the debt component, and the associated non-cash interest expense.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt
        instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing
        the effective interest method.</font></div>
    <div><br>
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  </div>
  <div id="TRGRSegment:a1cf4e84-8de1-45da-9d35-f8021125f40b">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Segment information</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have two operating segments, our Ionis
          Core segment and Akcea Therapeutics, our majority-owned affiliate. Akcea is </font>a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases<font style="font-size: 10pt;
          font-family: 'Times New Roman', Times, serif;">. We provide segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker
          reviews to assess operating performance and to make operating decisions. We allocate a portion of Ionis&#8217; development, R&amp;D support and general and administrative expenses to Akcea for work Ionis performs on behalf of Akcea.</font></font></div>
    <div><br>
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  </div>
  <div id="TRGRSegment:eb0cb11b-f5c5-41c2-abb0-19c90b201cf3">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-based compensation expense</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, restricted
        stock units, or RSUs, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation
        expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures
        differ from those estimates.</font></div>
    <div><br>
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  </div>
  <div id="TRGRSegment:6e9eb1c6-09d1-4896-a9b5-77e7804a4cc9">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The
      expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the three months ended March 31, 2019 and 2018, we
      used the following weighted-average assumptions in our Black-Scholes calculations:</div>
    <div><br>
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    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Ionis Employee Stock Options:</font></div>
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        <tr>
          <td style="width: 70.68%; vertical-align: bottom;">&#160;</td>
          <td style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;" colspan="5">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 70.68%; vertical-align: bottom;">&#160;</td>
          <td style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2019</font></div>
          </td>
          <td style="width: 2.66%; vertical-align: bottom;">&#160;</td>
          <td style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Risk-free interest rate</font></div>
          </td>
          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2.4%</font></div>
          </td>
          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2.2%</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
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          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
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          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Expected life</font></div>
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
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          <td style="width: 70.68%; vertical-align: bottom;">&#160;</td>
          <td style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;" colspan="5">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
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          <td style="width: 70.68%; vertical-align: bottom;">&#160;</td>
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            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2019</font></div>
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          <td style="width: 2.66%; vertical-align: bottom;">&#160;</td>
          <td style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
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            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Risk-free interest rate</font></div>
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1.6%</font></div>
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          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.0%</font></div>
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.0%</font></div>
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          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Volatility</font></div>
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">45.5%</font></div>
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
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          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Expected life</font></div>
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6 months</font></div>
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6 months</font></div>
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    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. RSUs vest annually over a four-year
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    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">16</font></div>
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        <tr>
          <td style="width: 70.68%; vertical-align: bottom;">&#160;</td>
          <td style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;" colspan="5">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
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          <td style="width: 70.68%; vertical-align: bottom;">&#160;</td>
          <td style="width: 13.37%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2019</font></div>
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          <td style="width: 2.66%; vertical-align: bottom;">&#160;</td>
          <td style="width: 13.3%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
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          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Risk-free interest rate</font></div>
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2.5%</font></div>
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
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          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Dividend yield</font></div>
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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        <tr>
          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Volatility</font></div>
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">77.1%</font></div>
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        <tr>
          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Expected life</font></div>
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
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          </td>
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    </table>
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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;">Akcea ESPP:</div>
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        <tr>
          <td style="width: 70.68%; vertical-align: bottom;">&#160;</td>
          <td style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;" colspan="5">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
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        <tr>
          <td style="width: 70.68%; vertical-align: bottom;">&#160;</td>
          <td style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2019</font></div>
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          <td style="width: 2.66%; vertical-align: bottom;">&#160;</td>
          <td style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
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        <tr>
          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Risk-free interest rate</font></div>
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          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2.5%</font></div>
          </td>
          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1.6%</font></div>
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        <tr>
          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Dividend yield</font></div>
          </td>
          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Volatility</font></div>
          </td>
          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">64.1%</font></div>
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">62.3%</font></div>
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        </tr>
        <tr>
          <td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Expected life</font></div>
          </td>
          <td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6 months</font></div>
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          <td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td>
          <td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6 months</font></div>
          </td>
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    </table>
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    </div>
  </div>
  <div id="TRGRSegment:ae31082c-3a91-41a9-9792-327ab44e68e3">
    <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 months ended March 31, 2019 and 2018 (in thousands). Our
      non-cash stock-based compensation expense includes $18.6 million and $6.4 million of stock-based compensation expense for Akcea employees for the three months ended March 31, 2019 and 2018, respectively.</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </font><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="zcf1605899b3f4dc5b064d0954801f6b7">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Cost of products sold</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">118</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Research, development and patent</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">24,435</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">19,682</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Selling, general and administrative</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">20,952</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,769</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">45,505</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">28,451</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:412abbbd-814c-4f71-aba9-474a94ce5071">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2019, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and
      RSUs was $192.2 million and $68.7 million, respectively. We will adjust total unrecognized compensation cost for future forfeitures. We expect to recognize the cost of non-cash stock-based compensation expense related to non-vested stock options and
      RSUs over a weighted average amortization period of 1.4 years and 2.0 years, respectively.</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:ec90ad6c-7dcf-4a96-a86e-03cb2bb343f2">
    <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impact of recently issued accounting standards</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain
        other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its
        lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. The new standard is effective for annual and
        interim periods beginning after December 15, 2019. Early adoption is permitted for periods beginning after December 15, 2018. When we adopt the new standard, we will make any adjustments to beginning balances through a cumulative-effect adjustment
        to accumulated deficit on that date. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it will have on our condensed consolidated financial statements and disclosures.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing
        arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The
        update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. The updated guidance is effective for fiscal years beginning after December 31, 2019, and interim periods within those
        fiscal years. Early adoption is permitted in any interim period. We are currently assessing the effects this updated guidance could have on our condensed consolidated financial statements and timing of adoption.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2018, the FASB updated its disclosure requirements related to Level 1, 2 and 3 fair value measurements. The
        update included deletion and modification of certain disclosure requirements and additional disclosure related to Level 3 measurements. The guidance is effective for fiscal years beginning after December 31, 2019 and early adoption is permitted. We
        adopted this updated guidance on January 1, 2019 and it did not have a significant impact on our disclosures.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">17</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <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: left;"><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and
        the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we will implement it (in italics):</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="ze2378cc95caf41a8812996d32ce9adb6" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1)</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z49336f40311d4e24a686a91024d7bb62" class="DSPFListTable">

            <tr>
              <td style="width: 72pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">We will apply all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a
                    customer</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z38f59eba5ea64835be5aebfb61e1b9de" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2)</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Adds &#8220;unit of account&#8221; concept to collaboration accounting guidance to align with Topic 606. The &#8220;unit of account&#8221; concept is used to determine if revenue is
                    recognized or if a contra expense is recognized from consideration received under a collaboration</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z5a731f0510b74784875c6c7b969f4d5e" class="DSPFListTable">

            <tr>
              <td style="width: 72pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">We will use the &#8220;unit of account&#8221; concept when we receive consideration under a collaboration to determine when we recognize revenue or a
                    contra expense</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z7d2b5c4d6aac42c59cd8be6d773c6de6" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3)</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer
                    and is not directly related to the sales to third parties</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z48ed9f8017a849c1b29917fc5909ade1" class="DSPFListTable">

            <tr>
              <td style="width: 72pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we will not
                    recognize revenue for the transaction</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The updated guidance is effective for public entities for fiscal years beginning after December 15, 2019, and interim
        periods within those fiscal years. Early adoption is permitted. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it will have on our condensed consolidated financial statements and disclosures.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:2e29b0ee-d4ee-467d-8965-211aa5fd111d">
    <div style="text-align: justify; text-indent: 0.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3.&#160; Investments</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">As of March 31, 2019, we had invested our excess cash primarily in debt instruments of the U.S. Treasury, financial
        institutions, corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#8217;s, Standard &amp; Poor&#8217;s, or S&amp;P, or Fitch, respectively. We have established guidelines
        relative to diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:d10a8f39-143d-41be-baa6-8b576a40764f">
    <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 March 31, 2019:</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="z6e2b2b49a0d648cda955a506ba424898">

        <tr>
          <td style="width: 83.04%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">One year or less</font></div>
          </td>
          <td style="width: 16.96%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">74%</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 83.04%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">After one year but within two years</font></div>
          </td>
          <td style="width: 16.96%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">21%</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 83.04%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">After two years but within three years</font></div>
          </td>
          <td style="width: 16.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">5%</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 83.04%; vertical-align: bottom; background-color: rgb(255, 255, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total</font></div>
          </td>
          <td style="width: 16.96%; vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">100%</font></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:76d66939-62f1-4369-8029-1b5d14a6d2ea">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As illustrated above, at March 31, 2019, 95 percent of our available-for-sale securities had a maturity of less than two years.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">All of our available-for-sale 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At March 31, 2019, we had an ownership interest of less than 20 percent in four private companies and two public companies
        with which we conduct business. The privately-held companies are Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd. The publicly-traded companies are ProQR and ATL.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:c6fe4c71-ac53-467b-a3af-8039e30edcc8">
    <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 style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </font><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="za0fe0a6aa2bd4d589ddff293f819d45d">

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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;" rowspan="1" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" rowspan="1" colspan="2"></td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" rowspan="1" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Gross Unrealized</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" rowspan="1" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" rowspan="1" colspan="2"></td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" rowspan="1" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" rowspan="1">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31, 2019</font></div>
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          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" rowspan="1" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" rowspan="1" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Cost </font>(1)</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" rowspan="1" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Gains</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Losses</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" rowspan="1" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" rowspan="1" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Estimated Fair Value</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" rowspan="1" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Available-for-sale securities:</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Corporate debt securities (2)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">869,483</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">326</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(531</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">869,278</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by U.S. government agencies</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">124,744</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">71</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(15</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">124,800</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by the U.S. Treasury (2)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">328,340</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">110</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(12</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">328,438</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by states of the U.S. and political subdivisions of the states</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">63,366</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">10</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(203</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">63,173</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Other municipal debt securities</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,931</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,932</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: 13.5pt; margin-left: 4.5pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total securities with a maturity of one year or less</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,388,864</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">518</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(761</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,388,621</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Corporate debt securities</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">360,976</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,236</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(336</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">361,876</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by U.S. government agencies</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">120,341</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">279</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(112</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">120,508</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by the U.S. Treasury</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">33,569</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(22</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">33,559</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by states of the U.S. and political subdivisions of the states</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">15,615</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(125</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">15,490</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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: 13.5pt; margin-left: 4.5pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total securities with a maturity of more than one year</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">530,501</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,527</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(595</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">531,433</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total available-for-sale securities</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,919,365</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,045</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,356</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,920,054</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Equity securities:</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total equity securities included in other current assets (3)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,212</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(244</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">968</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total available-for-sale and equity securities</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,920,577</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,045</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,600</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,921,022</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">18</font></div>
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    <div><br>
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    <div><br>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" rowspan="1"></td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" rowspan="1" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" rowspan="1" colspan="2"></td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" rowspan="1" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Gross Unrealized</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" rowspan="1" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" rowspan="1" colspan="2"></td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" rowspan="1" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" rowspan="1">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">December 31, 2018</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" rowspan="1" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" rowspan="1" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Cost </font>(1)</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" rowspan="1" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Gains</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Losses</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" rowspan="1" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" rowspan="1" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Estimated Fair Value</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" rowspan="1" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Available-for-sale securities:</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Corporate debt securities</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">956,879</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">13</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,858</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">955,034</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by U.S. government agencies</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">168,839</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(104</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">168,738</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by the U.S. Treasury</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">244,640</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">15</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(77</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">244,578</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">63,572</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(323</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">63,249</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">31</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(2,362</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,431,599</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Corporate debt securities</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">299,018</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">194</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,286</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">297,926</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by U.S. government agencies</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">107,789</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">194</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(109</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">107,874</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by the U.S. Treasury</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">15,600</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(24</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">15,576</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by states of the U.S. and political subdivisions of the states</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">16,980</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(287</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">16,693</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total securities with a maturity of more than one year</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">439,387</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">388</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,706</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">438,069</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total available-for-sale securities</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,873,317</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">419</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(4,068</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,869,668</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Equity securities:</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total equity securities included in other current assets (3)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,212</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">137</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,349</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total available-for-sale and equity securities</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,874,529</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">556</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(4,068</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,871,017</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zeb54d66835344fdcab81c08445af6cb2" class="DSPFListTable">

            <tr>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1)</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our available-for-sale securities are held at amortized cost.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z6bbde37eb4ca4d3094e71c6e2f485e7c" class="DSPFListTable">

            <tr>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(2)</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Includes investments classified as cash equivalents on our condensed consolidated balance sheet.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zcee61ce0a197408c9434d43fd94b53a2" class="DSPFListTable">

            <tr>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(3)</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize our equity securities at 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 on our condensed consolidated balance sheet.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:d5aff314-aef1-4877-a95b-aa9419cb3efd">
    <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 March 31, 2019. 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. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full
      recovery of our debt securities&#8217; amortized cost basis at maturity.</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zd639f5b124a643039b6b7db454bc28c9">

        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 30%;">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Less than 12 Months of</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Temporary Impairment</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">More than 12 Months of</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Temporary Impairment</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Total Temporary</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Impairment</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 30%;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;(In thousands)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Number of</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Investments</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Estimated</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Fair Value</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Unrealized</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Losses</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Estimated</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Fair Value</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Unrealized</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Losses</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Estimated</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Fair Value</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Unrealized</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Losses</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 30%; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Corporate debt securities</font></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: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">275</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">530,786</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(306</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">102,815</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(561</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">633,601</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(867</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 30%; background-color: rgb(255, 255, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by U.S. government agencies</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">24</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">91,005</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(81</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">16,534</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(46</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">107,539</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(127</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 30%; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by the U.S. Treasury</font></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: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">15</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">94,603</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(34</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">94,603</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(34</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 30%; padding-bottom: 2px; background-color: rgb(255, 255, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by states of the U.S. and political subdivisions of the states</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">39</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">11,254</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(9</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">51,579</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(319</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">62,833</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(328</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 30%; padding-bottom: 4px; background-color: rgb(204, 238, 255);">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total temporarily impaired securities</font></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: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">353</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">727,648</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(430</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">170,928</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(926</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">898,576</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,356</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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    </table>
    <div><br>
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  </div>
  <div id="TRGRSegment:cbe1216a-7f75-4ff9-bf74-5a33ea09d28c">
    <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4.&#160; Fair Value Measurements</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers
        include: Level 1, defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity
        securities in publicly-held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified
        as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify the majority of our securities as Level 2. We obtain the fair
        value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service
        provider and comparing that fair value to the fair value based on observable market prices.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:7a9615d1-174e-4092-868e-4143ff1a651c">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following tables present the major security types we
        held at March 31, 2019 and December 31, 2018 that we regularly measure and carry at fair value. At March 31, 2019 and December 31, 2018, </font>our ProQR investment was <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">subject
        to trading restrictions that extend through the fourth quarter of 2019, as a result we</font> included a lack of marketability discount in valuing this investment,</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">19</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">which is a Level 3 input.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> The amount we owned in ProQR did not
          change from December 31, 2018 to March 31, 2019. The tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</font></font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zf3118d61425148388cfc511e52692fec">

        <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">At</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31, 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Quoted Prices in</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Active Markets</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(Level 1)</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Significant Other</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Observable Inputs</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(Level 2)</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Significant Unobservable Inputs</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(Level 3)</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Cash equivalents (1)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">146,542</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">146,542</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Corporate debt securities (2)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,231,154</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,231,154</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by U.S. government agencies (3)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">245,308</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">245,308</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by the U.S. Treasury (4)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">361,997</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">361,997</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by states of the U.S. and political subdivisions of the states (3)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">78,663</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">78,663</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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></div>
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div>
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Other municipal debt securities (3)</font></div>
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          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,932</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,932</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div>
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Investment in ProQR Therapeutics N.V. (5)</font></div>
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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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">968</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">968</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; 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%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" 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: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,067,564</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">508,539</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,558,057</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">968</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z6768a13b4a2349bd9bc49ecd5d12b6e8">

        <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">At</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">December 31, 2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Quoted Prices in</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Active Markets</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Significant Other</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Significant Unobservable Inputs</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(Level 3)</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Cash equivalents (1)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">146,281</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">146,281</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Corporate debt securities (6)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,252,960</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,252,960</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by U.S. government agencies (3)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">276,612</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">276,612</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by the U.S. Treasury (7)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">260,154</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">260,154</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by states of the U.S. and political subdivisions of the states (3)</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">79,942</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">79,942</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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></div>
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div>
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Investment in ProQR Therapeutics N.V. (5)</font></div>
            </div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,349</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,349</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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: justify; text-indent: -8.9pt; margin-left: 22.55pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,017,298</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">406,435</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,609,514</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,349</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z4685f050227f44ebab3244e85f09cbb8" class="DSPFListTable">

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

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(2) $27.1 million was included in cash and cash equivalents on our condensed consolidated balance
        sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z27d2c26d68c743cf8112458711f76ce5" class="DSPFListTable">

            <tr>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(3)</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Included in short-term investments on our condensed consolidated balance sheet.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z2107c14101f84df08ded926f89ef874b" class="DSPFListTable">

            <tr>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(4)</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$15.0 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on
                    our condensed consolidated balance sheet.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z0edcda02ea7e4f64a538011a212fd7d8" class="DSPFListTable">

            <tr>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(5)</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Included in other current assets on our condensed consolidated balance sheet.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z3ab1088d3636453bb2d6fd37d72bc887" class="DSPFListTable">

            <tr>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(6)</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$50.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on
                    our condensed consolidated balance sheet.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z265647ba509a4cfc86c3419448fcdd3c" class="DSPFListTable">

            <tr>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(7)</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$14.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on
                    our condensed consolidated balance sheet.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:ce3749d2-0332-4b7f-90e2-af64292c1ef1">
    <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Convertible Notes</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our 1 percent notes had a fair value of $928.4 million at March 31, 2019. 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.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:58a4b720-ec4c-463e-9611-cb7dc16ed3ad">
    <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; Operating Leases</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:cc583128-75a3-426e-bb35-25bf83223032">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing
      facility. We lease this space under a non-cancelable operating lease with an initial term ending in June 2021 and an option to extend the lease for up to two five-year periods.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We also lease additional office space and we sublease a portion of this space to Akcea. We lease this space under a
        non-cancelable operating lease with an initial term ending in June 2023 and an option to extend the lease for one five-year period. The sublease with Akcea is eliminated in our condensed consolidated financial statements.</font></div>
    <div><br>
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    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">20</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
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    </div>
    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea entered into an operating lease agreement for office space located in Boston, Massachusetts for its new corporate
        headquarters in the second quarter of 2018. The lease commencement date was in August 2018 and Akcea took occupancy in September 2018. Akcea is leasing this space under a non-cancelable operating lease with an initial term ending after 123 months
        and an option to extend the lease for an additional five-year term. Under the lease agreement, Akcea received a three-month free rent period, which commenced on August 15, 2018, and a tenant improvement allowance up to $3.8 million. Akcea provided
        the lessor with a letter of credit to secure its obligations under the lease in the initial amount of $2.4 million, to be reduced to $1.8 million on the third anniversary of the rent commencement date and to $1.2 million on the fifth anniversary of
        the rent commencement date if Akcea meets certain conditions set forth in the lease at each such time.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases we
        did not include the extension options for these leases.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:00fa3a4a-f7d9-4a57-8906-ad0a390c86c1">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="ze2c4dad5d9a743468ab9097105aa5885">

        <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">At March 31, 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Right-of-use operating lease assets (1)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">13.1</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Operating lease liabilities (2)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">18.0</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Weighted average remaining lease term</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="2">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">9 years</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Weighted average discount rate</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">7.6</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z5cee89a6ed2042ba9bd2381e1149f4dd" class="DSPFListTable">

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

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="ze2b07e7ceac74c84a06c694b053068ec" class="DSPFListTable">

            <tr>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(2)</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Current portion of $2.0 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference
                    included in long-term obligations.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:c7507401-8a5b-4609-828e-60f45841cab1">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We paid cash of $1.0 million for rent payments we made during the three months ended March 31, 2019, which was included in the
      measurement of our lease liabilities in our net cash provided by operating activities in our condensed consolidated statement of cash flows.</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:d32cd15b-9645-4f24-a077-2bd0b090cb3c">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2019, the payments for our operating lease liabilities are as follows (in thousands):</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="zc9b017a57cd745b496e9fa004fa840d5">

        <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</font> <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</font></font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Remainder of 2019</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,341</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Years ending December 31,</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
            <div style="text-align: justify; margin-left: 18.7pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3,008</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;">
            <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2021</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,725</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
            <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2022</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,539</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;">
            <div style="text-align: justify; margin-left: 18.7pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2023</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,505</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Thereafter</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">11,862</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;">
            <div style="text-align: left; margin-left: 18.7pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total minimum lease payments</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">24,980</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Less:</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; margin-left: 18.7pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Imputed interest</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(7,020</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;">
            <div style="text-align: left; margin-left: 36.7pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total operating lease liabilities</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">17,960</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:c08496f2-f3e8-45c9-964e-f8032509258e">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Rent expense was $0.9 million for the three months ended March 31, 2019 and was negligible for the three months ended March 31, 2018.</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:5572f4c4-aef7-4dc3-80b0-2c8c976bcb2d">
    <div style="text-align: left; text-indent: -45pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6.&#160; Income Taxes</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 24.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our effective tax rate may vary from the U.S. federal statutory tax rate due to the change in the mix of earnings in tax
        jurisdictions with different statutory rates, benefits related to tax credits, and the tax impact of non-deductible expenses and other permanent differences between income before income taxes and taxable income.&#160; Our effective income tax rate of
        25.5 percent for the three months ended March 31, 2019 differed from the U.S. federal statutory rate of 21 percent primarily due to state taxes, partially offset by the tax benefit related to estimated research &amp; development and orphan drug
        credits and the excess tax benefit related to share-based compensation.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recorded income tax expense of $31 million
          for the three months ended March 31, 2019, compared to $15,000 </font>for the same period in 2018. The increase in our income tax expense was primarily due to our expectation that we will generate U.S. federal and state taxable income in 2019.
        Our 2019 income tax expense has two components. The first component relates to federal income taxes. We expect to utilize our deferred tax assets to offset our U.S. federal taxable income. We are recording non-cash income tax expense as we utilize
        our federal deferred tax assets.&#160;The other component of our income tax expense relates to the estimated cash taxes we will pay for our state income taxes. Although we are recording the expense for our state income taxes in 2019, we will not have to
        make the majority of the payment for this liability until the first quarter of 2020.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:d0f42ed5-1ed2-4751-99bc-29ded22a29a6">
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">21</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7.&#160; Collaborative Arrangements and Licensing Agreements</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Below, we have included our collaborations with substantive changes during the first three months of 2019 from those
        included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2018.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Strategic Partnership</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:70998ad4-5681-47a6-8b0e-4de9bd62fa38">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Biogen</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have several strategic collaborations with
          Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological
          disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. In</font> December 2017, we entered into a collaboration with Biogen to identify <font style="background-color:
          #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense medicines for the treatment of SMA</font>. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, we and Biogen are
          currently developing six other medicines to treat neurodegenerative diseases under these collaborations, including tofersen (formerly IONIS-SOD1</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">) for
          ALS patients with SOD1 mutations, or SOD1-ALS, which Biogen moved into a Phase 3 study in the first quarter of 2019, IONIS-MAPT</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx </sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for Alzheimer&#8217;s
          disease</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">,</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> IONIS-C9</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx </sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for ALS patients with C9ORF72
          mutations, and IONIS-BIIB6</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, IONIS-BIIB7</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and
          IONIS-BIIB8</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to treat undisclosed neurodegenerative diseases. In addition to these medicines, we and Biogen are evaluating numerous additional targets
          to develop medicines to treat neurological diseases. In April 2018, we entered into a new strategic collaboration for the treatment of neurological diseases with Biogen. From inception through March 2019, we have received over $2.1 billion from
          our Biogen collaborations, including $1 billion we received from Biogen in the second quarter of 2018 for our 2018 strategic neurology collaboration.</font></font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:c6b84a7e-2176-4548-94c8-99a91fdb28d2">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions,
      except percentage amounts):</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="z6c0f4970591e4dc184d8f0030172470b">

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          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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;" colspan="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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">
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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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">41.1</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D revenue</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
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          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
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          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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: 27pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total revenue from our relationship with Biogen</font></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">
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          </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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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">
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          </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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Percentage of total revenue</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">28</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">36</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:604dd18c-84dc-4acd-ae5a-4ec04c513649">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the first quarter of 2019, we did not have any changes to our performance obligations or the timing in which we expect to
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    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In April 2019, we achieved a $7.5 million milestone payment from Biogen, when we advanced a new target for an unidentified
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our condensed consolidated balance sheet at March 31, 2019 and <font style="font-size: 10pt; font-family: 'Times New
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    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:093a34d3-54ca-439a-8b9e-3704d5bfe9f0">
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Commercialization Partners</div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:7ee40f5c-0c39-498c-b39d-6f14e706629c">
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:6393f559-ec7b-4c3d-aaa8-a28f5ea99857">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Roche</div>
    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have two collaborations with Roche, one to
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    <div><br>
    </div>
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  <div id="TRGRSegment:ca09fc5e-8ab4-45af-8e88-29c7e6e70e0b">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions,
      except percentage amounts):</div>
    <div><br>
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    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="zf02bc343b536400ebf24803a350d008e">

        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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;" colspan="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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: -27pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D revenue</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">41.2</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2.0</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Percentage of total revenue</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">14</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div>
          </td>
        </tr>

    </table>
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  </div>
  <div id="TRGRSegment:4eb24571-ce3d-4bb8-bc90-d1c5fa25e993">
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    </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;">Our revenue in the first quarter of 2019, included $35 million of milestone payments we earned when Roche dosed the first patient in the
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    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">During the first quarter of 2019, we did not have any changes to our performance obligations or the timing in which we
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    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our condensed consolidated balance sheet at March 31, 2019 and <font style="font-size: 10pt; font-family: 'Times New
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    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:cac34e65-7994-48b8-b6af-d4b9c42fdb22">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Akcea Collaboration</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following collaboration agreement relates to Akcea, our majority owned affiliate. Our consolidated results include all
        the revenue earned and cash received under this collaboration agreement. We reflect the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock in a separate line on the statement of operations and a separate line within
        stockholders&#8217; equity in our condensed consolidated balance sheet.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Novartis</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2017, we and Akcea initiated a
          collaboration with Novartis to develop and commercialize AKCEA-APO(a)-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and AKCEA-APOCIII-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt;
          font-family: 'Times New Roman', Times, serif;">.</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">&#160;</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the collaboration agreement, Novartis has an exclusive option to further develop and
          commercialize AKCEA-APO(a)-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and AKCEA-APOCIII-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.
          Akcea is responsible for completing a Phase 2 program, conducting an end-of-Phase 2 meeting with the FDA and providing initial quantities of API for each medicine. If Novartis exercises an option for either of these medicines, Novartis will be
          responsible for all further global development, regulatory and co-commercialization activities and costs for such medicine. </font>In the first quarter of 2019, Novartis licensed AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>. Novartis is responsible for
        conducting and funding all future development, regulatory and commercialization activities for AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>, including a global pivotal cardiovascular outcomes study, for which planning and initiation activities are underway. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through March 2019, we have received over $330 million from our Novartis collaboration, including $150 million we earned from Novartis in the first quarter of
          2019 for the license of AKCEA-APO(a)-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>. Akcea paid us $75 million as a sublicense fee in 2.8 million shares of Akcea common stock.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We identified a new performance obligation when we granted Novartis the license of AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> in the
        first quarter of 2019 because the license is distinct from our other performance obligations. We recognized the $150 million license fee for AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> as revenue at that time because Novartis had full use of the license without
        any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Novartis.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea is responsible for the development activities under this collaboration. As such, Akcea is recognizing the associated
        revenue in its statement of operations, and we reflect all of Akcea&#8217;s revenue in our consolidated results. Akcea pays us sublicense fees for payments that it receives under the collaboration and we recognize those fees as revenue in our Ionis Core
        operating segment results and Akcea recognizes the fees as R&amp;D expense. In our consolidated results, we eliminate this sublicense revenue and expense. Any cash Akcea receives is included in our condensed consolidated balance sheet.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:0b79ca62-954b-45d2-a9c3-7348e773bac4">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Novartis (in millions,
      except percentage amounts):</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="zaa471ae35d5f4afe8a944834192fc8e4">

        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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;" colspan="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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: -27pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D revenue</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">157.1</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">17.1</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Percentage of total revenue</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">53</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:4f2ef415-0deb-4be6-bba8-e8d78851f7cc">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the first quarter of 2019, we did not have any changes to our performance obligations, except as noted above, or the timing in
      which we expect to recognize revenue under our Novartis collaboration.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our condensed consolidated balance sheet at March 31, 2019 and December 31, 2018 included deferred revenue of $23.3
        million and $28.8 million, respectively, related to our relationship with Novartis.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:56d9c5fa-6b33-4139-a271-bcc6acf7eaff">
    <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8.&#160; Segment Information</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have two reportable segments Ionis Core
          and Akcea Therapeutics. </font>At <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">March 31, 2019 </font>we owned approximately 76 percent of Akcea.<font style="font-size: 10pt; font-family: 'Times New Roman',
          Times, serif;"> Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.</font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In our Ionis Core segment we are exploiting our antisense technology to generate a broad pipeline of first-in-class and/or
        best-in-class medicines for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">23</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea is </font>a biopharmaceutical company
        focused on developing and commercializing medicines to treat patients with rare and serious diseases<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Akcea generates revenue from TEGSEDI product sales and from its
          collaborations with Novartis and PTC Therapeutics.</font></font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:e9aca296-be8e-4f81-97cd-cb26002be75a">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables show our segment revenue and income (loss) from operations for the three months ended March 31, 2019 and March 31,
      2018 (in thousands), respectively.</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zd1e216a5057a4ee2923a0a499084b4fa">

        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended March 31, 2019</font></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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Ionis Core</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea Therapeutics</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Elimination of</font></div>
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          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Total</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue:</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top;">
            <div style="text-align: left; margin-left: 7.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Commercial revenue:</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; background-color: #CCEEFF;">
            <div style="text-align: left; margin-left: 25.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA royalties</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">59,711</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">59,711</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; background-color: #FFFFFF;">
            <div style="text-align: left; margin-left: 25.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI product sales, net</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6,754</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6,754</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; margin-left: 25.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Licensing and other royalty revenue</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,623</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,623</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; 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: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; margin-left: 43.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total commercial revenue</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">61,334</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6,754</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">68,088</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; margin-left: 7.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D revenue under collaborative agreements</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">160,556</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">157,062</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(88,492</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">229,126</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; margin-left: 25.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total segment revenue</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">221,890</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">163,816</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(88,492</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">297,214</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total operating expenses</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">114,515</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">137,610</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(76,446</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">175,679</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Income from operations</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">107,375</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">26,206</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(12,046</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">121,535</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended March 31, 2018</font></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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Ionis Core</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea Therapeutics</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Elimination of</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Total</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
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            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue:</font></div>
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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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>
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            <div style="text-align: left; margin-left: 7.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Commercial revenue:</font></div>
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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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: top; width: 52%; background-color: #CCEEFF;">
            <div style="text-align: left; margin-left: 25.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA royalties</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">41,081</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">41,081</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; margin-left: 25.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Licensing and other royalty revenue</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">942</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">942</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; margin-left: 43.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total commercial revenue</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">42,023</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">42,023</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; margin-left: 7.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D revenue under collaborative agreements</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">90,517</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">17,108</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(5,229</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">102,396</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;">
            <div style="text-align: left; margin-left: 25.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total segment revenue</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">132,540</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">17,108</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(5,229</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">144,419</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total operating expense</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">105,544</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">47,435</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(5,259</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">147,720</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Income (loss) from operations</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">26,996</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(30,327</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">30</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(3,301</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following table shows our total assets by segment at March 31, 2019 and December 31, 2018 (in thousands),
        respectively.</font></div>
    <div><br>
    </div>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Total Assets</font></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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Ionis Core</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea Therapeutics</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Elimination of</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Intercompany Activity</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Total</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">March 31, 2019</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3,112,235</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">458,717</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(735,063</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,835,889</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, 2018</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,975,491</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">365,261</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(672,968</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,667,784</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:bd424805-4e9b-4bc8-a3ce-16d99b6ff1b2">
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zbfb6124362fa4d4aabde193795b58a49" class="DSPFListTable">

            <tr>
              <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 2</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">MANAGEMENT&#8217;S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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 majority owned affiliate, Akcea Therapeutics, Inc.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Forward-Looking Statements</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">In addition to historical information contained in this Report on Form 10-Q, the Report includes
        forward-looking statements regarding our business and the therapeutic and commercial potential of SPINRAZA (nusinersen), TEGSEDI (inotersen), WAYLIVRA (volanesorsen) and our technologies and products in development, including the business of Akcea
        Therapeutics, Inc., our majority-owned affiliate. 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, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business
        around such drugs. 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, 2018, which is on file with the
        U.S. Securities and Exchange Commission and is available from us, and those identified within Part II Item 1A. Risk Factors of this Report. Although our forward-looking statements reflect the good faith judgment of our management, these statements
        are based only on facts and factors currently known by us. As a result, you are cautioned not to rely on these forward-looking statements.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">24</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Overview</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are a leader in discovering and developing RNA-targeted therapeutics with sustained and growing revenues. We have
        created an efficient and broadly applicable drug discovery platform leveraging our expertise in antisense oligonucleotide therapeutics that we believe has fundamentally changed medicine and transformed the lives of people with devastating and often
        deadly diseases. Our large, diverse and advanced pipeline of over 40 first-in-class and/or best-in-class medicines addresses diseases across a broad range of therapeutic areas, targeting small, medium and large patient populations.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have three commercial medicines approved in major markets around the world, SPINRAZA, TEGSEDI and WAYLIVRA. We have two
        medicines in Phase 3 studies, IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>,<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">&#160;</sub>for Huntington&#8217;s disease, and tofersen<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">, </sub>for SOD1-ALS. We also have the potential for two more medicines to begin Phase 3 studies this year and the potential for a total of
        10 medicines in Phase 3 studies by the end of 2020. These medicines, along with the more than 30 additional medicines in our pipeline, represent multiple potential drivers of value for years to come. We believe our efficient drug discovery
        platform, coupled with our innovation-centric business model, provides us with the flexibility to determine the optimal development and commercialization strategy to maximize the commercial opportunity for each of our medicines and ensure that we
        continue to produce transformative medicines for patients who need them. We believe we are positioned to drive substantial value for patients and shareholders.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">As of March 2019, SPINRAZA was approved in over 40 countries around the world, and our partner Biogen, who is responsible
        for global SPINRAZA commercial activities, reported that more than 7,500 patients are now on SPINRAZA therapy. In addition, Biogen plans to continue to pursue regulatory filings in additional countries. SPINRAZA is the first and only approved
        medicine for the treatment of SMA. SPINRAZA is the established standard-of-care for all people with this progressive, debilitating and often fatal genetic disease. In November 2018, SPINRAZA was recognized with the 2018 International Prix Galien
        award as Best Biotechnology Product. This prestigious honor marks the seventh Prix Galien award for SPINRAZA. To date, we have earned more than $410 million in commercial revenues from royalties on sales of SPINRAZA.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI, a once weekly, self-administered subcutaneous medicine, was approved in 2018 in the U.S., EU and Canada for the
        treatment of polyneuropathy caused by hATTR in adult patients. hATTR is a debilitating, progressive, and fatal disease. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea, our majority-owned affiliate focused on
          developing and commercializing medicines to treat patients with rare and serious diseases, </font>launched TEGSEDI globally in late 2018. Our aim is to make TEGSEDI available globally. We plan to achieve this in part through Akcea&#8217;s exclusive
        license agreement with PTC to commercialize TEGSEDI in Latin America. In January 2019, PTC filed an application for regulatory approval in Brazil with ANVISA, the Brazilian regulatory authority. ANVISA granted priority review for TEGSEDI. We have
        earned $9 million in TEGSEDI product sales since launching late last year.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">WAYLIVRA, a self-administered, </font>subcutaneous
        medicine,<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> received conditional marketing authorization from the European Commission, or EC, as an adjunct to diet in adult patients with genetically confirmed FCS and at
          high risk for pancreatitis in May 2019. We and Akcea are preparing to commercialize WAYLIVRA in the EU and we are also focused on regulatory discussions in the U.S and Canada. Akcea plans to leverage its existing commercial infrastructure in
          Europe to market WAYLIVRA. </font>Akcea is continuing to conduct open-label extension and early access programs.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We are also developing WAYLIVRA for the treatment of
          people with familial partial lipodystrophy, or FPL.&#160;People with FPL lack subcutaneous adipose tissue and have abnormal subcutaneous fat distribution causing increased incidence of potentially life-threatening pancreatitis, diabetes, extreme
          insulin resistance and increased liver fat.&#160;</font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In addition to commercializing TEGSEDI and preparing to commercialize WAYLIVRA, Akcea is developing four other
        clinical-stage medicines: AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx </sub>(TQJ230), AKCEA-ANGPTL3-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>, AKCEA-APOCIII-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> and <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">AKCEA-TTR-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </font>each of which could potentially treat multiple patient populations. Moving these medicines into Akcea allows us to retain substantial value from these medicines and
        ensures our core focus remains on innovation.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> As of March 2019, we owned approximately 76 percent of Akcea.</font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are continuously advancing our technology and pipeline to provide the most value to patients. We have a pipeline of
        over 40 medicines that, like SPINRAZA, TEGSEDI and WAYLIVRA, have the potential to transform the treatment of diseases with no adequate treatment today. These medicines range from treatments for rare diseases with small patient populations to more
        common diseases afflicting millions of patients. Our pipeline covers a broad spectrum of therapeutic areas, such as cardiometabolic diseases, neurodegenerative diseases, cancer, severe and rare diseases and others. We believe our large and diverse
        pipeline contains many near-, mid- and longer-term growth drivers for the company.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The depth of our knowledge and expertise with
          antisense technology together with our strong financial position provides us the flexibility to partner our medicines at what we believe is the optimal time to maximize the value of our medicines. </font>We have a distinct partnering strategy
        based on each specific medicine and the expertise and resources we and our potential partners may bring to a collaboration. We may develop and commercialize some medicines through affiliates. In general, these are medicines, like TEGSEDI and
        WAYLIVRA, that can benefit from our internal expertise and infrastructure, have manageable development plans and costs, and have the potential for initial rare disease indications. For other medicines, <font style="font-size: 10pt; font-family:
          'Times New Roman', Times, serif;">we may establish collaborations to advance the medicine. We have alliances with a cadre of leading global pharmaceutical companies that are working alongside us in developing our medicines, advancing our
          technology, preparing to commercialize our medicines and selling our medicines. Our partners include the following companies, among others: AstraZeneca, Bayer, Biogen, GSK, Janssen, Novartis and Roche. Our partners bring resources and expertise
          that augment and build upon our internal capabilities.</font> We have the potential to earn over $20 billion in future milestone payments and licensing fees from our existing partnerships.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">25</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Financial Highlights</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our financial results (in thousands):</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="z543d250b0b404675bf6104c6b6c2d9d2">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total revenue</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">297,214</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">144,419</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total operating expenses</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">175,679</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">147,720</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Income (loss) from operations</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">121,535</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(3,301</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net income (loss)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">90,884</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(10,812</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">84,443</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,420</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our revenue for the three months ended March 31, 2019 of $297.2 million increased significantly compared to the same
        period in 2018, primarily from the $150 million license fee we earned from Novartis when it licensed AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> and a more than 45 percent increase in commercial revenue from SPINRAZA royalties.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our operating expenses for <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the first quarter
          of 2019</font> of $<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">175.7</font> million increased over the same period in 2018. The increase in operating expenses was principally due to our investments in the global
        launch of <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI</font>.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">During the first quarter of 2019 we received more than $270 million in payments from our partners, including $150 million
        from Novartis, $78 million from Biogen and $35 million from Roche. This is compared to more than $155 million received in the first quarter of 2018. We believe our strong financial position should enable us to continue to execute on our corporate
        goals throughout 2019 and beyond.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Recent Business Highlights</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"> (Q1 2019 and subsequent activities)</font></font></div>
    <div style="text-align: left;"><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zb7122c678b7b4034bd35f751c7dc15eb" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SPINRAZA &#8211; the worldwide standard-of-care for the treatment
                      of people with all forms of spinal muscular atrophy</font></font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zb36eb9b4c59c42ff8a93fe25aa4a668d" class="DSPFListTable">

            <tr>
              <td style="width: 54pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen reported worldwide sales of SPINRAZA of $518 million in the first quarter of 2019, a 42 percent increase compared to Q1 2018, driven primarily by
                    increased penetration in existing markets, new country launches and continued uptake in the U.S. by children and adult patients.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z81830849dc6d45c29f392d78e9096f1b" class="DSPFListTable">

            <tr>
              <td style="width: 54pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">There were more than 7,500 SMA patients from over 40 countries on SPINRAZA treatment at the end of the first quarter of 2019, including commercial patients
                    and patients in the expanded access program and clinical trials.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zfc4010ac4dec4b929539c0faccaecb09" class="DSPFListTable">

            <tr>
              <td style="width: 54pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA data from the ongoing NURTURE and SHINE open-label extension studies demonstrated continued durable efficacy and reinforced the safety profile of
                    SPINRAZA in patients treated for up to 6 years, as presented by Biogen at the 2019 AAN Annual Meeting.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z8a3b9516476743b5b2b44c32a728bd31" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">TEGSEDI &#8211; launch underway in multiple markets for the
                      treatment of polyneuropathy of hATTR</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"> in adult patients</font></font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zd5e238570c0d42b9b84c9d54ebda5501" class="DSPFListTable">

            <tr>
              <td style="width: 54pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI product sales were $7 million in its first full quarter on the market and $9 million since launching in Q4 2018.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zfbb022398d044e05a6c2a6887b34c956" class="DSPFListTable">

            <tr>
              <td style="width: 54pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI received a positive Final Evaluation Document, or FED, from the National Institute for Health and Care Excellence, or NICE, authorizing reimbursement
                    for the treatment of patients with polyneuropathy due to hATTR amyloidosis in England.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z95ceef1a269d4f178feb7c2fcc0a15a2" class="DSPFListTable">

            <tr>
              <td style="width: 54pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Data presented at AAN from the TEGSEDI NEURO-TTR open-label extension study demonstrated long-term efficacy and safety in patients with hATTR.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z3e9bc1b7d3554104b514d57ba2a1f23c" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">WAYLIVRA &#8211; approved in the EU for the treatment of adults
                      with genetically confirmed FCS at high risk for pancreatitis</font></font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z26e08e73c8a249b7b287d60d04e731e3" class="DSPFListTable">

            <tr>
              <td style="width: 54pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea&#8217;s preparations to launch in the EU are underway, beginning in Germany in Q3 2019.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zbca1a615cd1245688654daf533eb697c" class="DSPFListTable">

            <tr>
              <td style="width: 54pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Launch in additional EU countries is planned in 2020.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zaf4d87a4612a4564a50da5c93b0ec7df" class="DSPFListTable">

            <tr>
              <td style="width: 54pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Earned a $6 million milestone payment from PTC Therapeutics for the EU approval of WAYLIVRA.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z1b407039f66f4734bb956254d732b488" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Roche presented nine-month data from the ongoing Phase 1/2 open-label extension study of IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> in patients with Huntington&#8217;s disease at AAN,
                    demonstrating continued and sustained reductions in mutant huntingtin protein with bi-monthly dosing.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z3d8854e599484748a727fad9ddecb94c" class="DSPFListTable">

            <tr>
              <td style="width: 54pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Based on these data, Roche amended the dosing regimen in the Phase 3 study of IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> in patients with Huntington&#8217;s disease to replace the
                    monthly dosing regimen with a tri-annual (every four months) dosing regimen.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="za60047eaaee54b78b5afba5b6d072d54" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen presented data from the Phase 1/2 study of tofersen in SOD1-ALS patients at AAN, demonstrating improvements in clinical measures of ALS disease
                    progression after three months of treatment.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify; margin-left: 54pt; margin-bottom: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font><font style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt;" id="TRGRRTFtoHTMLTab">&#160;</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Tofersen is in a Phase 3 clinical study that could support a rapid path to patients.</font></div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zc54d2fd6f9c2491c846e62df74327ce5" class="DSPFListTable">

            <tr>
              <td style="width: 54pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen is collaborating with regulators to further define the scope of the clinical data package required to support registration.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z47e7ab5c9b0c48659124862bf22fe9dd" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generated a $7.5 million milestone payment for advancing a new target for an unidentified neurological disease under our 2018 strategic neurology
                    collaboration with Biogen.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zbb0a89eca4e4454c8855af7d569e414f" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Brett P. Monia, Ph.D., our chief operating officer was appointed to our board of directors.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">26</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Critical Accounting Policies</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font 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. 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 our audit committee of our
        board of directors. In the following paragraphs, we describe the specific risks associated with these critical accounting policies and we caution that future events rarely develop exactly as one may expect, and that best estimates may require
        adjustment.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The significant accounting policies, which we believe are the most critical to aid in fully understanding and evaluating
        our reported financial results, require the following:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z4357a1799a8447bb8ea359d74a127512" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Assessing the propriety of revenue recognition and associated deferred revenue;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z3db7c4e3066c4dc986b74fc2358bc46f" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Valuing premiums received under our collaborations;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z30d71bb58ac54cb7a3cbadbb2a26286f" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Determining the proper valuation of investments in marketable securities;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zae3a053f72d6493bb064cbcc589f91e4" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities; and</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zc7044c169cba44a9b9b215673787a2c4" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accounting for income taxes.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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, 2018.</font></div>
    <div><br>
    </div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Results of Operations</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Revenue</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total revenue for the three months ended March 31, 2019 was $297.2 million compared to $144.4 million for the same period
        in 2018 and was comprised of the following (amounts in thousands):</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zb177789976f24748b7dc491f30686b7b">

        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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;" colspan="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue:</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Commercial revenue:</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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: -27pt; margin-left: 45pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA royalties</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">59,711</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6,754</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: rgb(204, 238, 255); padding-bottom: 2px;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,623</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D revenue:</font></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">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">35,851</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">28,011</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">40,017</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6,329</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">License fees</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">150,000</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">61,678</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Other services</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3,258</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6,378</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 45pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total R&amp;D revenue</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">229,126</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">102,396</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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: 81pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total revenue</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">297,214</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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">
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          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">144,419</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the first quarter of 2019, we significantly increased both commercial revenue and R&amp;D revenue. Commercial revenue
        from SPINRAZA royalties increased over 45 percent. We also added growing TEGSEDI product sales to our commercial revenue.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our R&amp;D revenue substantially increased in the first quarter of 2019 due to the $150 million license fee we earned
        from Novartis when it licensed AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> and $35 million we earned from Roche when it enrolled the first patient in the Phase 3 study of IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> in patients with Huntington&#8217;s disease.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the second quarter of 2019, Alnylam announced it licensed our technology to Regeneron. Once the transaction closes, we
        expect to earn $20 million in sublicensing revenue.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating Expenses</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Operating expenses for the three months ended March 31, 2019 were $175.7 million, and increased compared to $147.7 million
        for the same period in 2018. Our operating expenses increased year over year principally due to our investment in the global launch of TEGSEDI. Stock-based compensation expense increased year over year primarily due to the increase in the grant
        date fair value of Akcea options granted and from stock option grants made to new employees as Akcea continued to build out its organization.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">27</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
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    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our operating expenses by segment were as follows (in thousands):</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="za9c58a0444a74785b0aafd96bb35f060">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Ionis Core</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">78,514</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">83,476</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea Therapeutics</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">128,106</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">41,052</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Elimination of intercompany activity</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(76,446</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(5,259</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Subtotal</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">130,174</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">119,269</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">45,505</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">28,451</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total operating expenses</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">175,679</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">147,720</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 is not indicative of our operating results or cash flows from our operations. Further, we internally evaluate the
        performance of our operations excluding it.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Cost of Products Sold</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our cost of products sold consisted of manufacturing costs, including certain fixed costs, transportation and freight,
        indirect overhead costs associated with the manufacturing and distribution of TEGSEDI and certain associated period costs. We do not expect our fixed costs will increase in direct correlation to TEGSEDI product sales. We expensed a significant
        portion of the cost of producing TEGSEDI that Akcea is using in the commercial launch as R&amp;D expense prior to the regulatory approval of TEGSEDI. We expect cost of products sold to increase as we deplete these inventories.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our cost of products sold by segment were as follows (in thousands):</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="ze04efd4a79f44b22b467f75c779f141d">

        <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
        </tr>
        <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Ionis Core</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea Therapeutics</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,326</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Elimination of intercompany activity</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,403</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Subtotal</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">923</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">118</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total cost of products sold</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,041</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For the three months ended March 31, 2019, our cost of products sold was $0.9 million. We began recognizing cost of
        products sold in the third quarter of 2018 when TEGSEDI was approved. We previously recognized $0.3 million of costs we incurred to produce the amount of TEGSEDI we sold in the first quarter of 2019. We recognized these costs prior to the first
        quarter of 2019 because we incurred these costs before we obtained regulatory approval. We did not have cost of products sold in the first quarter of 2018. Akcea includes the amortization for milestone payments it made to us related to the U.S. and
        European approvals of TEGSEDI in its cost of products sold. Akcea is recognizing this amortization over TEGSEDI&#8217;s remaining estimated patent life. We eliminate this amortization in our consolidated results. All amounts exclude non-cash compensation
        expense related to equity awards.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Research, Development and Patent Expenses</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our research, development and patent expenses consist of expenses for antisense drug discovery, antisense drug
        development, manufacturing and operations and R&amp;D support expenses.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following table sets forth information on research, development and patent expenses (in thousands):</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="z5f25058a792844238f9faa7dcabd9ab4">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Research, development and patent expenses, excluding non-cash compensation expense related to
                equity awards</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">81,982</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">84,385</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">24,435</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">19,682</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total research, development and patent expenses</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">106,417</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">104,067</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our research, development and patent expenses by segment were as follows (in thousands):</font></div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="z9660fab212af4dda885a3f514388d8b4">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Ionis Core</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">61,327</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">63,988</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea Therapeutics</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">95,698</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">25,657</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Elimination of intercompany activity</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(75,043</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(5,259</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Subtotal</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">81,982</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">84,386</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">24,435</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">19,682</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total research, development and patent expenses</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">106,417</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">104,068</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">28</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For the three months ended March 31, 2019, our total research, development and patent expenses were $82.0 million compared
        to $84.4 million for the same period in 2018. All amounts exclude non-cash compensation expense related to equity awards.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Antisense Drug Discovery</u></font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We use our proprietary antisense technology to generate information about the function of genes and to determine the value
        of genes as drug discovery targets. We use this information to direct our own antisense drug discovery research, and that of our partners. Antisense drug discovery is also the function that is responsible for advancing our antisense core
        technology.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">As we continue to advance our antisense technology, we are investing in our drug discovery programs to expand our and our
        partners&#8217; drug pipelines. Our antisense drug discovery expenses are part of our Ionis Core business segment.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our antisense drug discovery expenses were as follows (in thousands) and are part of our Ionis Core business segment:</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="z2924bb3331424b659081cffae3eeeb49">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Antisense drug discovery expenses, excluding non-cash compensation expense related to equity awards</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">14,632</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">13,905</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">5,493</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">4,376</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total antisense drug discovery expenses</font></div>
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          <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">
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">20,125</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">18,281</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Antisense drug discovery expenses for the three months ended March 31, 2019 were $14.6 million, and were slightly higher
        compared to $13.9 million for the same period in 2017, due to expenses we incurred related to advancing our early stage research programs. All amounts exclude non-cash compensation expense related to equity awards.</font></div>
    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Antisense Drug Development</u></font></font></div>
    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following table sets forth drug development expenses, including the breakdown for medicines in Phase 3 development
        and/or commercialization for which we have incurred significant costs (in thousands):</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="z5d1ce5952d324c52ae7acb0b37d4de19">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">WAYLIVRA</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,971</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6,401</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">4,691</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">5,836</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Other antisense development projects</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">22,310</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">20,653</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Development overhead expenses</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">18,944</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">17,110</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total antisense drug development, excluding non-cash compensation expense related to equity awards</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">47,916</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">50,000</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12,234</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,858</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total antisense drug development expenses</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">60,150</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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">
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          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">58,858</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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    </table>
    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Antisense drug development expenses were $47.9 million for the three months ended March 31, 2019, and decreased slightly
        compared to $50.0 million for the same period in 2018. All amounts exclude non-cash compensation expense related to equity awards.</font></div>
    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our antisense drug development expenses by segment were as follows (in thousands):</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="zc261ce1f98b9423493c224dedf2b7c97">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Ionis Core</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">29,070</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">30,972</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea Therapeutics</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">19,028</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Elimination of intercompany activity</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(75,000</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Subtotal</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">47,916</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">50,000</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12,234</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,858</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total antisense drug development expenses</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">60,150</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">58,858</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the $75 million
        sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>. Akcea recognized the $75 million sublicense fee in its R&amp;D development expenses. We eliminated this expense in our consolidated results.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 products 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 product. Although we may characterize a product 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.</font></div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">29</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Instead, we allocate our internal resources on a shared basis across numerous products based on each product&#8217;s particular needs at that time.
        This means we are constantly shifting resources among products. Therefore, what we spend on each product during a particular period is usually a function of what is required to keep the products progressing in clinical development, not what
        products 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 product to another and cannot be used to accurately predict future costs for each product. And, because we always have numerous medicines in preclinical and early stage
        clinical research, the fluctuations in expenses from medicine to medicine, in large part, offset one another. If we partner a medicine, it may affect the size of a trial, its timing, its total cost and the timing of the related costs.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Manufacturing and Operations</u></font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Expenditures in our manufacturing and operations function consist primarily of personnel costs, specialized chemicals for
        oligonucleotide manufacturing, laboratory supplies and outside services. Our manufacturing and operations function is responsible for providing drug supplies to antisense drug development, Akcea and our collaboration partners. Our manufacturing
        procedures include testing to satisfy good laboratory and good manufacturing practice requirements.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our manufacturing and operations expenses were as follows (in thousands):</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="z0e67bae041314b3cbaa4397d00d70cc0">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Manufacturing and operations expenses, excluding non-cash compensation expense related to equity
                awards</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">10,154</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12,309</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,057</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,402</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total manufacturing and operations expenses</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12,211</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">14,711</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Manufacturing and operations expenses were $10.2 million for the three months ended March 31, 2019 and decreased compared
        to $12.3 million for the same period in 2018. Manufacturing and operations expenses decreased primarily related to manufacturing costs we expensed for TEGSEDI in the first quarter of 2018 that did not recur in the first quarter of 2019 because upon
        approval in mid-2018, we now capitalize all TEGSEDI manufacturing costs into inventory and recognize these expenses into cost of products sold as we sell TEGSEDI. All amounts exclude non-cash compensation expense related to equity awards.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our manufacturing and operations expenses by segment were as follows (in thousands):</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="z58d5d8593c294807a409067847797b23">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Ionis Core</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,799</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">11,642</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea Therapeutics</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,355</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">5,896</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; 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>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(5,229</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Subtotal</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">10,154</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12,309</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,057</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,402</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; 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: 76%; padding-bottom: 4px; background-color: #FFFFFF;">
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" 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: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12,211</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
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            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">14,711</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>R&amp;D Support</u></font></font></div>
    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In our research, development and patent expenses, we include support costs such as rent, repair and maintenance for
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    <div><br>
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    <div><br>
    </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>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
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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="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
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          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Personnel costs</font></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">
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3,910</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3,103</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Occupancy</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,177</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,759</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Patent expenses</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">523</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">701</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Depreciation and amortization</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">121</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">101</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Insurance</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">411</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">470</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Other</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,138</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,038</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
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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">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">9,280</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,172</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
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          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">4,651</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">4,046</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total R&amp;D support expenses</font></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">
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">13,931</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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">
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12,218</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D support expenses for the three months ended March 31, 2019 were $9.3 million, and increased slightly compared to
        $8.2 million for the same period in 2018. All amounts exclude non-cash compensation expense related to equity awards.</font></div>
    <div><br>
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    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">30</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our R&amp;D support expenses by segment were as follows (in thousands):</font></div>
    <div><br>
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    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="zf4e520c5f7a84c2480ace6cb05ddf909">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Ionis Core</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,826</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">7,470</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea Therapeutics</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">497</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">732</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Elimination of intercompany activity</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(43</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(30</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
          </td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Subtotal</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">9,280</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,172</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">4,651</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">4,046</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total R&amp;D support expenses</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">13,931</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12,218</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Selling, General and Administrative Expenses</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Selling, general and administrative expenses include personnel and outside costs associated with the pre-commercialization
        and commercialization activities for our medicines and costs to support our company, our employees and our stockholders including, legal, human resources, investor relations, and finance. Additionally, we include in selling, general and
        administrative expenses such costs as rent, repair and maintenance of buildings and equipment, depreciation and utilities costs that we need to support the corporate functions listed above. We also include fees we owe under our in-licensing
        agreements related to SPINRAZA.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following table sets forth information on selling, general and administrative expenses (in thousands):</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="zb951265efc2d422797e34a329ea39551">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Selling, general and administrative expenses, excluding non-cash compensation expense related to
                equity awards</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">47,269</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">34,884</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">20,952</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,769</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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          <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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total selling, general and administrative expenses</font></div>
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          <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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">68,221</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
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          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">43,653</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
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    </table>
    <div><br>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Selling, general and administrative expenses
          were $47.3 million for the three months ended March 31, 2019, and increased compared to $34.9 million for the same period in 2018. </font>The increase in SG&amp;A expenses was principally due to the cost of commercializing <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI. All amounts exclude non-cash compensation expense related to equity awards.</font></font></div>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our selling, general and administrative expenses by segment were as follows (in thousands):</font></div>
    <div><br>
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    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="zf7b9eb90e44747c58bb3be611d7eeda1">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Ionis Core</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">17,187</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">19,488</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea Therapeutics</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">30,082</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">15,396</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Subtotal</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">47,269</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">34,884</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">20,952</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,769</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total selling, general and administrative expenses</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">68,221</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">43,653</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Akcea Therapeutics, Inc.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following table sets forth information on&#160;operating expenses (in thousands) for our Akcea Therapeutics business
        segment:</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="zcd27298eda944e149e0986cb008426bf">

        <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="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Cost of products sold</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,326</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Development and patent expenses</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">95,698</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">25,656</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Selling, general and administrative expenses</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">30,082</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">15,396</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Profit/loss share for TEGSEDI commercialization activities</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(9,056</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total operating expenses, excluding non-cash compensation expense related to equity awards</font></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">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">119,050</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">41,052</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash compensation expense related to equity awards</font></div>
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          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">18,560</font></div>
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          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6,383</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total Akcea Therapeutics operating expenses</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">137,610</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">47,435</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Operating expenses for Akcea were $119.1 million for the three months ended March 31, 2019, and increased compared to
        $41.1 million for the same period in 2018.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the third quarter of 2018, Akcea began recognizing cost of products sold expenses after the approval of TEGSEDI.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">31</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea&#8217;s development and patent expenses increased for the three months ended March 31, 2019, compared to the same period
        in 2018 as a result of the one-time $75 million sublicense fee it paid to Ionis in Akcea common stock for Ionis' portion of the license fee Akcea received from Novartis in the first quarter of 2019.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea&#8217;s SG&amp;A expenses increased in the three months ended March 31, 2019 compared to the same period in 2018,
        primarily because Akcea was continuing to build its commercial infrastructure and advance commercialization activities necessary to successfully launch TEGSEDI and WAYLIVRA. For each period presented, we allocated a portion of Ionis&#8217; SG&amp;A
        expenses to Akcea for work we performed on Akcea&#8217;s behalf. We include these allocated expenses in Akcea&#8217;s SG&amp;A expenses in the table above. All amounts exclude non-cash compensation expense related to equity awards.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the first quarter of 2019, we began sharing profits and losses for TEGSEDI with Akcea under our TTR licensing
        agreement. As Akcea is the principal for all commercial activities related to the TTR License Agreement, Akcea records all activities related to TEGSEDI on a gross basis in its statement of operations based on the nature of the activity, including
        revenues, cost of products sold and sales and marketing expenses. Ionis&#8217; share of the net profit/loss from commercializing TEGSEDI is separately presented on Akcea&#8217;s statement of operations on the line titled &#8220;Profit/loss share for TEGSEDI
        commercialization activities&#8221;. This represents the amount Ionis owes Akcea under the licensing agreement for its share of the net profit/loss of TEGSEDI commercialization activities during the period. For the three months ended March 31, 2019,
        profit/loss share for TEGSEDI commercialization activities was $9.1 million. We eliminate this amount in our consolidated results.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">All amounts exclude non-cash compensation expense related to equity awards.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Investment Income</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Investment income for the three months ended March 31, 2019 was $12.1 million compared to $3.6 million for 2018. The
        increase in investment income was primarily due to a higher average cash balance and an improvement in the market conditions during the three months ended March 31, 2019 compared to the same period in 2018.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Interest Expense</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Interest expense for the three months ended March 31, 2019 was $11.6 million and increased slightly compared to $10.9
        million for the same period in 2018.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following table sets forth information on interest expense (in thousands):</font></div>
    <div><br>
    </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>
          <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Convertible notes:</font></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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" 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" nowrap="nowrap" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
            <div style="text-align: left; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Non-cash amortization of the debt discount and debt issuance&#160;costs</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">9,200</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,524</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: 9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Interest expense payable in cash</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,714</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,714</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Interest on mortgage for primary R&amp;D and manufacturing facilities</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">582</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">594</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Other</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">103</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">106</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" 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: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total interest expense</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">11,599</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">10,938</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Income Tax Expense</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recorded income tax expense of $31 million
          for the three months ended March 31, 2019, compared to $15,000 </font>for the same period in 2018. The increase in our income tax expense was primarily due to our expectation that we will generate U.S. federal and state taxable income in 2019.
        Our 2019 income tax expense has two components. The first component relates to federal income taxes. We expect to utilize our deferred tax assets to offset our U.S. federal taxable income. We are recording non-cash income tax expense as we utilize
        our federal deferred tax assets.&#160;The other component of our income tax expense relates to the estimated cash taxes we will pay for our state income taxes. Although we are recording the expense for our state income taxes in 2019, we will not have to
        make the majority of the payment for this liability until the first quarter of 2020.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Net Income (Loss)</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We reported net income of $90.9 million for the three months ended March 31, 2019, compared to a net loss of $10.8 million
        for the same period in 2018. Our net income was primarily due to increased revenue year-over-year.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Net (Income) Loss Attributable to Noncontrolling Interest in Akcea Therapeutics, Inc.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At March 31, 2019, we owned approximately 76 percent of Akcea. The shares of Akcea third parties own represent an interest
        in Akcea's equity that we do not control. However, because we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our consolidated financial statements.
        We reflect the noncontrolling interest attributable to other owners of Akcea's common stock in a separate line called &#8220;Net loss attributable to noncontrolling interest in Akcea&#8221; on our statement of operations. Our noncontrolling interest in Akcea
        on our statement of operations for the three months ended March 31, 2019, was income of $6.4 million, compared to a loss of $9.4 million for same period in 2018.&#160;</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">32</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Net Income (Loss) Attributable to Ionis Pharmaceuticals, Inc. Common Stockholders<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and Net Income (Loss) per Share</font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We had net income attributable to our common stockholders&#8217; of $84.4 million for the <font style="font-size: 10pt;
          font-family: 'Times New Roman', Times, serif;">three months ended March 31, 2019</font>, compared to a net loss of $1.4 million for the same period in 2018. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Basic and
          diluted net income per share for the three months ended March 31, 2019 was $0.63 and $0.62, respectively. Our basic and diluted net loss per share for the three months ended March 31, 2018 were both $0.01.</font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Liquidity and Capital Resources</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have financed our operations primarily from research and development collaborative agreements. Beginning in December
        2016 we added commercial revenue from SPINRAZA royalties and in the third quarter of 2018 we added product sales from TEGSEDI. From our inception through March 31, 2019, we have earned approximately $3.5 billion in revenue.&#160;We also financed our
        operations through the sale of our equity securities and the issuance of long-term debt. From the time we were founded through March 31, 2019, we have raised net proceeds of approximately $1.8 billion from the sale of our equity securities, not
        including the $182.4 million Akcea received in net proceeds from its IPO in July 2017. Additionally, we have borrowed approximately $1.4 billion under long-term debt arrangements to finance a portion of our operations over the same time period.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At March 31, 2019, we had cash, cash equivalents and short-term investments of $2.3 billion and stockholders&#8217; equity of
        $1.4 billion. In comparison, we had cash, cash equivalents and short-term investments of $2.1 billion and stockholders&#8217; equity of $1.2 billion at December 31, 2018.&#160;Our cash, cash equivalents and short-term investments increased in the first
        quarter of 2019 primarily from payments we received from Novartis and Roche.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At March 31, 2019, we had consolidated working capital of $2.1 billion compared to $1.9 billion at December 31, 2018. As
        of March 31, 2019, our debt and other obligations totaled $776.1 million compared to $763.9 million at December 31, 2018. The increase in our debt and other obligations is from the operating lease liability we added to our balance sheet when we
        adopted the new accounting guidance for leases on January 1, 2019.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following table summarizes our contractual obligations as of March 31, 2019. 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:</font></div>
    <div><br>
    </div>
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          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</font></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;" colspan="18">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Payments Due by Period (in millions)</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
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        <tr>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Contractual Obligations</font></div>
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(selected&#160;balances&#160;described&#160;below)</font></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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Total</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Less than 1 year</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">1-3 years</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">3-5 years</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" 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;" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">After 5 years</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 40%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Convertible senior notes (principal and interest payable)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">706.0</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6.9</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">699.1</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 40%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Building mortgage payments</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">80.2</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2.4</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">4.8</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6.4</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">66.6</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 40%; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Financing arrangements (principal and interest payable)</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12.7</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">12.7</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 40%; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Other obligations (principal and interest payable)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1.0</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.1</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.1</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.1</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.7</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 40%; padding-bottom: 2px; background-color: #CCEEFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Operating leases</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">25.3</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3.2</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">5.8</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">5.1</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">11.2</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: bottom; width: 40%; padding-bottom: 4px; background-color: #FFFFFF;">
            <div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">825.2</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">25.3</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">709.8</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">11.6</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">78.5</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contractual obligations consist primarily of our convertible debt. In addition, we also have facility mortgages,
        facility leases, equipment financing arrangements and other obligations. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Due to the uncertainty with respect to the timing of future cash flows associated with our
          unrecognized tax benefits, we are unable to make reasonably reliable estimates of the period of cash settlement with the respective taxing authorities. Therefore, we have excluded our gross unrecognized tax benefits from our contractual
          obligations table above.</font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">1 Percent Convertible Senior Notes</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In November 2014, we completed a $500 million
          offering of convertible senior notes, which mature in 2021 and bear interest at 1 percent. </font>We used a substantial portion of the net proceeds from the issuance of the 1 percent convertible senior notes to repurchase $140 million in
        principal of our 2&#190; percent convertible senior notes. As a result, the principal balance of the 2&#190; percent notes following the repurchase in November 2014 was $61.2 million.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In December 2016, we issued an additional $185.5 million of 1 percent convertible senior notes in exchange for the
        redemption of $61.1 million of our 2&#190; percent convertible senior notes. At March 31, 2019, we had a nominal amount of our 2&#190; percent convertible senior notes outstanding. At March 31, 2019, we had the following 1 percent convertible senior notes
        outstanding (amounts in millions except price per share and interest rate data):</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" align="center" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;" id="z0b34688965d841c28ebbb49be2d52d1d">

        <tr>
          <td valign="bottom" style="vertical-align: top; padding-bottom: 2px; width: 70%;">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">1 Percent</font></div>
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Convertible Senior Notes</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 70%; background-color: rgb(204, 238, 255);">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Outstanding principal balance</font></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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 27%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">685.5</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; background-color: rgb(255, 255, 255); width: 70%;">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Original issue date ($500 million of principal)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; background-color: rgb(255, 255, 255); width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: top; background-color: rgb(255, 255, 255);" colspan="2">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">November 2014</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; background-color: rgb(255, 255, 255); width: 1%;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 70%;">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additional issue date ($185.5 million of principal)</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; background-color: rgb(204, 238, 255); width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="2">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 2016</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; background-color: rgb(204, 238, 255); width: 1%;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; background-color: rgb(255, 255, 255); width: 70%;">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Maturity date</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; background-color: rgb(255, 255, 255); width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: top; background-color: rgb(255, 255, 255);" colspan="2">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">November 2021</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; background-color: rgb(255, 255, 255); width: 1%;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 70%;">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Interest rate</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; background-color: rgb(204, 238, 255); width: 1%;" colspan="1">&#160;</td>
          <td valign="bottom" style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="2">
            <div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1 percent</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; background-color: rgb(204, 238, 255); width: 1%;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 70%; background-color: rgb(255, 255, 255);">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Conversion price per share</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
          <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 27%; background-color: rgb(255, 255, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">66.81</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 70%; background-color: rgb(204, 238, 255);">
            <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total shares of common stock subject to conversion</font></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: 27%; background-color: rgb(204, 238, 255);" colspan="1">
            <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">10.3</font></div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">33</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Interest is payable semi-annually. The notes are convertible under certain conditions, at the option of the note holders.
        We 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 1 percent notes prior to maturity, and no sinking fund is provided for them. Holders of the 1 percent notes may
        require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indenture governing the 1 percent notes, at a purchase price equal to 100 percent of the principal amount of the notes to be
        purchased, plus accrued and unpaid interest.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Financing Arrangements</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In June 2015, we entered into a five-year revolving line of credit agreement with Morgan Stanley Private Bank, National
        Association, or Morgan Stanley. We amended the credit agreement in February 2016 to increase the amount available for us to borrow. Under the amended credit agreement, Morgan Stanley will provide a maximum of $30 million of revolving credit for
        general working capital purposes. Any loans under the credit agreement have interest payable monthly in arrears at a borrowing rate based on our option of:</font></div>
    <div><br>
    </div>
    <div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z0fe62105db6442ecaf7a5df904b5f413" class="DSPFListTable">

          <tr>
            <td style="width: 58.5pt; vertical-align: top; align: right;">
              <div style="text-align: left; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(i)</font></div>
            </td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a floating rate equal to the one-month London Interbank Offered Rate, or LIBOR, in effect plus 1.25 percent per annum;</font></div>
            </td>
          </tr>

      </table>
    </div>
    <div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="za09bb0ef397742f89dc4566220750ad9" class="DSPFListTable">

          <tr>
            <td style="width: 58.5pt; vertical-align: top; align: right;">
              <div style="text-align: left; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(ii)</font></div>
            </td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a fixed rate equal to LIBOR plus 1.25 percent for a period of one, two, three, four, six, or twelve months as elected by us; or</font></div>
            </td>
          </tr>

      </table>
    </div>
    <div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z38fda512aabe4e67ad8493dec9cdbded" class="DSPFListTable">

          <tr>
            <td style="width: 58.5pt; vertical-align: top; align: right;">
              <div style="text-align: left; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(iii)</font></div>
            </td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a fixed rate equal to the LIBOR swap rate during the period of the loan.</font></div>
            </td>
          </tr>

      </table>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, we pay 0.25 percent per annum, payable quarterly in arrears, for any amount unused under the credit
        facility. As of March 31, 2019, we had $12.5 million in outstanding borrowings under the credit facility with a 2.31 percent fixed interest rate and a maturity date of September 2019, which we used to fund our capital equipment needs consistent
        with our historical practice to finance these costs.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The credit agreement includes customary affirmative and negative covenants and restrictions. We are in compliance with all
        covenants of the credit agreement.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Research and Development and Manufacturing Facilities</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In July 2017, we purchased the building that houses our primary R&amp;D facility for $79.4 million. We purchased our
        manufacturing facility in July 2017 for $14.0 million. We financed the purchase of our primary R&amp;D facility and manufacturing facility, with mortgage debt of $51.3 million and $9.1 million, respectively. Our primary R&amp;D facility mortgage
        has an interest rate of 3.88 percent. Our manufacturing facility mortgage has an interest rate of 4.20 percent. During the first five years of both mortgages we are only required to make interest payments. Both mortgages mature in August 2027.</font></div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Other Obligations</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In addition to contractual obligations, we had outstanding purchase orders as of March 31, 2019 for the purchase of
        services, capital equipment and materials as part of our normal course of business.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We plan to continue to enter into collaborations with partners to provide for additional revenue to us and we may incur
        additional cash expenditures related to our obligations under any of the new agreements we may enter into. We currently intend to use our cash, cash equivalents and short-term investments to finance our activities. However, we may also pursue other
        financing alternatives, like issuing additional shares of our common stock, issuing debt instruments, refinancing our existing debt, or securing lines of credit. Whether we use our existing capital resources or choose to obtain financing will
        depend on various factors, including the future success of our business, the prevailing interest rate environment and the condition of financial markets generally.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:dbfc58f5-f463-4bbe-97b7-14278d3b980f">
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z393cb4baf95b45a9bfd3dd96d96f2a2f" class="DSPFListTable">

            <tr>
              <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 3.</td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are exposed to changes in interest rates primarily from our long-term debt arrangements and, secondarily, 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, commodity prices, equity prices or other market changes that affect market risk sensitive instruments.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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. </font>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,<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font>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 consolidated financial statements. Our business strategy incorporates potentially significant
        international expansion, particularly related to TEGSEDI and WAYLIVRA, therefore we expect that the impact of foreign currency exchange rate fluctuations may become more substantial in the future.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:de0efc5f-8f3f-4bf4-8fa3-c5ddc838f058">
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">34</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <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: left;"><br>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z5abe56508ab24529ad15730f9a65ed55" class="DSPFListTable">

            <tr>
              <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 4.</td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">CONTROLS AND PROCEDURES</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 March 31, 2019. There have been no significant changes in our internal controls or in other factors that could significantly affect internal controls subsequent to March 31, 2019.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:4ab045ec-c90b-4bd3-ae7a-cc5f52f19624">
    <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 style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z761b123bc8724c5ebe8a2695478a5ccc" class="DSPFListTable">

            <tr>
              <td style="width: 72pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 1.</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">LEGAL PROCEEDINGS</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Not applicable.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:3b15db91-71c8-4aa5-8cea-ccde7e2d1cef">
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z7e03200470cd42d888698cf04afc160a" class="DSPFListTable">

            <tr>
              <td style="width: 72pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM
                  1A.</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">RISK FACTORS</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Investing in our securities involves a high degree of risk. You should consider carefully 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, 2018.</font></div>
    <div><br>
    </div>
    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Risks Associated with our Ionis Core and Akcea Therapeutics Businesses</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If the market does not accept our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, we are not likely to generate
        revenues or become consistently profitable.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Even if our medicines are authorized for marketing, including SPINRAZA, TEGSEDI and WAYLIVRA, our success will depend upon
        the medical community, patients and third-party payors accepting our medicines as medically useful, cost-effective and safe. Even when the FDA or foreign regulatory authorities authorize our or our partners&#8217; medicines for commercialization, doctors
        may not prescribe our medicines to treat patients. We and our partners may not successfully commercialize additional medicines.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, in many of the markets where we may sell our medicines in the future, if we cannot agree with the government
        regarding the price we can charge for our medicines, then we may not be able to sell our medicines in that market. Similarly, cost control initiatives by governments or third-party payors could decrease the price received for our medicines or
        increase patient coinsurance to a level that makes our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, unaffordable.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The degree of market acceptance for our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, depends upon a number of
        factors, including the:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z298b56b953fc4a42b23e357d9a55eaba" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">receipt and scope of marketing authorizations;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zde83f9e614df4e9c9aaebab16eb3d057" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">establishment and demonstration in the medical and patient community of the efficacy and safety of our medicines and their potential advantages over competing
                    products;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z56ffc7f41baa4eba845ea76c7d0dfe40" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">cost and effectiveness of our medicines compared to other available therapies;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z6a974523cd074231a1a30710c0fe219c" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">patient convenience of the dosing regimen for our medicines; and</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zb085ddb28b3f41509c7fabc7eb989564" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">reimbursement policies of government and third-party payors.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Based on the profile of our medicines, physicians, patients, patient advocates, payors or the medical community in general
        may not accept and/or use any medicines that we may develop.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">35</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <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: left;"><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, the product label for TEGSEDI in
          the U.S. has a boxed warning for thrombocytopenia and glomerulonephritis, requires periodic blood and urine monitoring, and TEGSEDI has a Risk Evaluation and Mitigation Strategy, or REMS, program. </font>Our main competition in the U.S. market
        for TEGSEDI is ONPATTRO (patisiran), marketed by Alnylam Pharmaceuticals, Inc. Although ONPATTRO requires intravenous administration and pre-treatment with steroids, it does not have a boxed warning or REMS. <font style="font-size: 10pt;
          font-family: 'Times New Roman', Times, serif;">Additionally, in the clinical studies with WAYLIVRA, declines in platelet counts were observed in many patients and some patients discontinued the studies because of platelet declines. The product
          label for WAYLIVRA requires periodic blood monitoring. In each case, these label requirements could negatively affect our ability to attract and retain patients for these medicines. We believe that the enhanced monitoring we have implemented to
          support early detection and management of these issues can help manage these safety issues so that patients can continue treatment. Since implementation of the enhanced monitoring, serious platelet events have been infrequent. While we believe we
          and Akcea can better maintain patients on TEGSEDI and WAYLIVRA through patient-centric commercial approaches where we plan to have greater involvement with physicians and patients, if we cannot effectively maintain patients on TEGSEDI or
          WAYLIVRA, we may not be able to generate substantial revenue from TEGSEDI or WAYLIVRA sales.</font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If we or our partners fail to compete effectively, our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, will not
        contribute significant revenues.*</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our competitors engage in drug discovery throughout the world, are numerous, and include, among others, major
        pharmaceutical companies and specialized biopharmaceutical firms. Other companies engage in developing antisense technology. Our competitors may succeed in developing medicines that are:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z2e4165e3f9a84dacbd5b0047887341b7" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">priced lower than our medicines;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z3dc42ace3fb64c0c9d2aa08a88727b16" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">reimbursed more favorably by government and other third-party payors than our medicines;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zfcdc9a30b2bd434aa6e7f475ace16ae9" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">safer than our medicines;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z8ff3c6c0c127475b841b6c80913d2825" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">more effective than our medicines; or</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zf6bbc2e960b14a649bcea53d1ed402c3" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">more convenient to use than our medicines.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">These competitive developments could make our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, obsolete or
        non-competitive.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Certain of our partners are pursuing other technologies or developing other medicines either on their own or in
        collaboration with others, including our competitors, to treat the same diseases our own collaborative programs target. Competition may negatively impact a partner&#8217;s focus on and commitment to our medicines and, as a result, could delay or
        otherwise negatively affect the commercialization of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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. Marketing and sales capability is another factor relevant to the competitive position of our medicines,
        and we will primarily rely on our partners and Akcea to provide this capability.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">There are several pharmaceutical and biotechnology companies engaged in the development or commercialization of products
        against targets that are also targets of products in our development pipeline. For example, Zolgensma (AVXS-101), Risdiplam (RG7916), reldesemtiv and firdapse could compete with SPINRAZA, and ONPATTRO (approved in the U.S. and Europe for a similar
        indication as TEGSEDI), Tafamadis, AG10, CRX-1008 and vutrisiran could compete with TEGSEDI. Also, metreleptin and gemcabene could compete with WAYLIVRA, while laquinimod, OMS823, selistat, VX15, WVE-120101 and WVE-120102 could compete with
        IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>. Furthermore, arimoclomol could potentially compete with tofersen.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Following approval, our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA could be subject to regulatory limitations. *</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Following approval of a medicine, we and our partners must comply with comprehensive government regulations regarding the
        manufacture, marketing and distribution of drug products. We or our partners may not obtain the labeling claims necessary or desirable to successfully commercialize our drug products, including SPINRAZA, TEGSEDI and WAYLIVRA.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The FDA and foreign regulatory authorities have the authority to impose significant restrictions on an approved drug
        product through the product label and on advertising, promotional and distribution activities. For example:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z5292b5ccd7004da7bc017189ec1c3589" class="DSPFListTable">

            <tr>
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              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the U.S., TEGSEDI&#8217;s label contains a boxed warning for thrombocytopenia and glomerulonephritis;</font></div>
              </td>
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        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zf0a93537e0c24175b3cd57ade82f60a0" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI requires periodic blood and urine monitoring; and</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zaf5da8ebb2844da1a7457e892ff9451e" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in the U.S. TEGSEDI is available only through a Risk Evaluation and Mitigation Strategy, or REMS, program.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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.&#160; If the results of such post-marketing studies are not satisfactory, the FDA or a foreign regulatory authority may withdraw marketing
        authorization or may condition continued marketing on commitments from us or our partners that may be expensive and/or time consuming to fulfill.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">36</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 39.6pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If we or others identify side effects after any of our drug products are on the market, or if manufacturing problems
        occur subsequent to regulatory approval, we or our partners may lose regulatory approval, or we or our partners may need to conduct additional clinical studies and/or change the labeling of our drug products, including <font style="font-size:
          10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA, TEGSEDI and WAYLIVRA.</font></font></div>
    <div><br>
    </div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">We depend on our collaboration with Biogen for the development and commercialization of SPINRAZA.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have entered into a collaborative arrangement with Biogen to develop and commercialize SPINRAZA. We entered into this
        collaboration primarily to:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z071d52cdedfb4a2bafab5decb15fdabf" class="DSPFListTable">

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              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fund our development activities for SPINRAZA;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z18067af6c06e4230ad3cbda39403996d" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">seek and obtain regulatory approvals for SPINRAZA; and</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z6f6319770d334d3da6462aee4e616fdd" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">successfully commercialize SPINRAZA.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are relying on Biogen to obtain additional regulatory approvals for SPINRAZA, and successfully commercialize SPINRAZA.
        In general, we cannot control the amount and timing of resources that Biogen devotes to our collaboration. If Biogen fails to further develop SPINRAZA, obtain additional regulatory approvals for SPINRAZA, or commercialize SPINRAZA, or if Biogen&#8217;s
        efforts are not effective, our business may be negatively affected.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our collaboration with Biogen may not continue for various reasons. Biogen can terminate our collaboration at any time. If
        Biogen stops developing or commercializing SPINRAZA, we would have to seek or spend additional funding, and SPINRAZA&#8217;s commercialization may be harmed or delayed.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our collaboration with Biogen may not result in the continued successful commercialization of SPINRAZA. If Biogen does not
        continue to successfully commercialize SPINRAZA, we will receive limited revenues for SPINRAZA.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If Akcea cannot optimize and maintain effective marketing and sales capabilities or enter into agreements with
        third&#160;parties to market and sell TEGSEDI and WAYLIVRA, we may not generate significant product&#160;revenue from TEGSEDI or WAYLIVRA.*</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">To successfully commercialize TEGSEDI Akcea must successfully manage its marketing, sales and distribution capabilities or
        make arrangements with third parties to perform these services. Akcea may not be successful in doing so. To commercialize TEGSEDI and WAYLIVRA in the initial indications Akcea is pursuing, Akcea will need to optimize and maintain a specialty sales
        force in each global region it expects to market TEGSEDI and WAYLIVRA, supported by case managers, reimbursement specialists, partnerships with specialty pharmacies, injection training, routine blood and urine monitoring and a medical affairs team.
        Akcea may seek to further penetrate markets by expanding its sales force or through strategic partnerships with other pharmaceutical or biotechnology companies or third-party sales organizations.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Even though certain members of Akcea&#8217;s management team and other employees have experience commercializing drug products,
        Akcea has no prior experience marketing, selling or distributing drug products, and there are significant risks involved in building and managing a commercial infrastructure. It will be expensive and time consuming for Akcea to maintain its own
        sales force and related compliance protocols to market TEGSEDI. Akcea may never successfully optimize or manage this capability and any failure could preclude the successful commercialization of TEGSEDI. Akcea and its partners, if any, will have to
        compete with other companies to recruit, hire, train, manage and retain marketing and sales personnel.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea incurred expenses prior to the launch of TEGSEDI and WAYLIVRA to integrate and manage the associated marketing and
        sales infrastructure. If regulatory requirements or other factors cause the commercial launch of TEGSEDI or WAYLIVRA to be less successful than expected, Akcea will have incurred expenses for having invested in these capabilities prior to realizing
        any significant revenue from sales of TEGSEDI or WAYLIVRA. Akcea&#8217;s sales force and marketing teams may not successfully commercialize TEGSEDI or WAYLIVRA.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">To the extent we and Akcea decide to rely on third parties to commercialize TEGSEDI or WAYLIVRA in a particular geographic
        market, such as the collaboration Akcea has with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America, we may receive less revenue than if Akcea commercialized TEGSEDI or WAYLIVRA by itself. Further we would have less control
        over the sales efforts of any other third parties involved in commercializing TEGSEDI or WAYLIVRA.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If Akcea cannot effectively build and manage its distribution, medical affairs, market access, marketing and sales
        infrastructure, or find a suitable third party to perform such functions, the commercial launch and sales of TEGSEDI may be delayed, less successful or precluded. Such events may result in decreased sales and lower revenue, which could have a
        material adverse effect on our business, prospects, financial condition and results of operations.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If government or other third-party payors fail to provide adequate coverage and payment rates for our medicines, including
        SPINRAZA, TEGSEDI and WAYLIVRA, our revenue will be limited.</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> </font><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 payors. The majority of people 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 drug products 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.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">37</font></div>
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    </div>
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    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Third-party payors, 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 drug products exists among third-party payors. Therefore, coverage and reimbursement for drug products can differ significantly
        from payor to payor. Further, we believe that future coverage and reimbursement will likely be subject to increased restrictions both in the U.S. and in international markets. For example, in the U.S., recent health reform measures have resulted in
        reductions in Medicare and other healthcare funding, and there have been several U.S. Congressional inquiries and proposed federal legislation designed to, among other things, reform government program reimbursement methodologies for drug products
        and bring more transparency to drug pricing. Third-party coverage and reimbursement for our products or 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If Biogen cannot manufacture finished drug product for SPINRAZA or the post-launch supply of the active drug substance for
        SPINRAZA, SPINRAZA may not maintain commercial success.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen is responsible for the long-term supply of both SPINRAZA drug substance and finished drug product. Biogen may not
        be able to reliably manufacture SPINRAZA drug substance and drug product to support the long-term commercialization of SPINRAZA. If Biogen cannot reliably manufacture SPINRAZA drug substance and drug product, SPINRAZA may not maintain commercial
        success, which will harm our ability to generate revenue.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If we or our partners fail to obtain regulatory approval for our medicines and additional approvals for SPINRAZA, TEGSEDI
        and WAYLIVRA, we or our partners cannot sell them in the applicable markets.*</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We cannot guarantee that any of our medicines will be considered safe and effective, or will be approved for
        commercialization. In addition, we cannot guarantee that SPINRAZA, TEGSEDI and WAYLIVRA will be approved in additional markets or for additional indications. We and our partners must conduct time-consuming, extensive and costly clinical studies to
        show the safety and efficacy of each of our medicines before they can be approved for sale. We must conduct these studies in compliance with FDA regulations and with comparable regulations in other countries.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We and our partners may not obtain necessary regulatory approvals on a timely basis, if at all, for our medicines. It is
        possible that regulatory agencies will not approve our medicines for marketing or additional marketing authorizations for SPINRAZA, TEGSEDI or WAYLIVRA. If the FDA or another regulatory agency believes that we or our partners have not sufficiently
        demonstrated the safety or efficacy of any of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, the agency will not approve the specific medicine or will require additional studies, which can be time consuming and expensive and which will
        delay or harm commercialization of the medicine. For example, Akcea received a CRL from the FDA and a preliminary notice of noncompliance withdrawal letter from Health Canada for WAYLIVRA. As result, Akcea may need to submit additional data to the
        FDA and Health Canada or conduct additional clinical studies before obtaining marketing authorization, which would be expensive and cause delays.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Failure to receive marketing authorization for our medicines, or failure to receive additional marketing authorizations
        for SPINRAZA, TEGSEDI or WAYLIVRA, or delays in these authorizations could prevent or delay commercial introduction of the medicine, and, as a result, could negatively impact our ability to generate revenue from product sales.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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.*</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Drug discovery and development has inherent risks and the historical failure rate for drugs is high. Antisense medicines
        are a relatively new approach to therapeutics. If we cannot demonstrate that our medicines are safe and effective for human use, we may need to abandon one or more of our drug development programs.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the past, we have invested in clinical studies of medicines that have not met the primary clinical end points in their
        Phase 3 studies. Similar results could occur in clinical studies for our medicines, including the study of WAYLIVRA in patients with FPL, the study of IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> in patients with Huntington&#8217;s disease and the study of tofersen in adults
        with SOD1-ALS. If any of our medicines in clinical studies, including WAYLIVRA, IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> and tofersen do not show sufficient efficacy in patients with the targeted indication, it could negatively impact our development and
        commercialization goals for these medicines and our stock price could decline.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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.*</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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, including the Phase 3 study of WAYLIVRA in patients with FPL, the study of IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> in patients with Huntington&#8217;s disease and the study of tofersen
        in adults with SOD1-ALS. There are a number of factors that could cause a clinical study to fail or be delayed, including:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z5a2583565431425eb88121d5a566b585" class="DSPFListTable">

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              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the clinical study may produce negative or inconclusive results;</font></div>
              </td>
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        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z280995e8d9504442930da5f7b7c2fcb6" class="DSPFListTable">

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              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">regulators may require that we hold, suspend or terminate clinical research for noncompliance with regulatory requirements;</font></div>
              </td>
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        </table>
      </div>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">38</font></div>
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    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zf39ea342ebc84ab4a8a36713c05b59c0" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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
                    in the trial;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z7a8a7d6d3a0a46e0b340184ce39668be" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">we may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z79f9a3daf1b14ecfad2728371222dda2" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">enrollment in our clinical studies may be slower than we anticipate;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z210a500f944c404892996049a768063f" class="DSPFListTable">

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

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zc21f4040950149f99115951a255f3720" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the cost of our clinical studies may be greater than we anticipate; and</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z60b2d56051b4406ab0ae2e25ff178828" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the supply or quality of our medicines or other materials necessary to conduct our clinical studies may be insufficient, inadequate or delayed.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In addition, our current medicines, including
          SPINRAZA, TEGSEDI and WAYLIVRA, are chemically similar to each other. As a result, a safety observation we encounter with one of our medicines could have, or be perceived by a regulatory authority to have, an impact on a different medicine we are
          developing.&#160;This could cause the FDA and other regulators to ask questions or take actions that could harm or delay our ability to develop and commercialize our medicines or increase our costs. For example, the FDA or other regulatory agencies
          could request, among other things, any of the following regarding one of our medicines: additional information or commitments before we can start or continue a clinical study, protocol amendments, increased safety monitoring, additional product
          labeling information, and post-approval commitments. Similarly, we have an ongoing Phase 3 study of WAYLIVRA in patients with FPL, an ongoing open-label extension study of WAYLIVRA in patients with FCS, an ongoing open-label extension study of
          TEGSEDI </font>and expanded access programs for each medicine.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Adverse events or results from these studies could negatively impact our current or planned marketing
          approval applications for WAYLIVRA in patients with FCS or the commercial opportunity for each product.</font></font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Any failure or delay in the clinical studies, including the Phase 3 study for WAYLIVRA in patients with FPL, the study of
        IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> in patients with Huntington&#8217;s disease and the study of tofersen in adults with SOD1-ALS, could reduce the commercial potential or viability of our medicines.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If we 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">To successfully commercialize any of our medicines, we or our partner would need to establish large-scale commercial
        manufacturing capabilities either on our own or through a third-party manufacturer. We and Akcea will rely on third-party manufacturers to supply the drug substance and drug product for TEGSEDI and WAYLIVRA. In addition, as our drug development
        pipeline increases and matures, we will have a greater need for clinical trial and commercial manufacturing capacity. 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 may not be able to manufacture our
        medicines at a cost or in quantities necessary to make commercially successful products.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Also, manufacturers, including us, must adhere to the FDA&#8217;s current Good Manufacturing Practices regulations and similar
        regulations in foreign countries, which the applicable regulatory authorities enforce through facilities inspection programs. We and our contract manufacturers may not comply or maintain compliance with Good Manufacturing Practices, or similar
        foreign regulations. Non-compliance could significantly delay or prevent receipt of marketing authorization for our medicines, including authorizations for SPINRAZA, TEGSEDI and WAYLIVRA, or result in enforcement action after authorization that
        could limit the commercial success of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">We depend on third parties to conduct our clinical studies for our medicines and any failure of those parties to fulfill
        their obligations could adversely affect our development and commercialization plans.*</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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, INC Research Toronto, Inc. and Medpace for the clinical
        studies for our medicines, including TEGSEDI and WAYLIVRA. We rely heavily on these parties for successful execution of our clinical studies, but do not control many aspects of their activities. For example, the investigators are not our employees.
        However, we are responsible for ensuring that these third parties conduct each of our clinical studies in accordance with the general investigational plan and approved protocols for the study. Third parties may not complete activities on schedule
        or may not conduct our clinical studies in accordance with regulatory requirements or our stated protocols. The failure of these third parties to carry out their obligations or a termination of our relationship with these third parties could delay
        or prevent the development, marketing authorization and commercialization of our medicines or additional authorizations for SPINRAZA, TEGSEDI and WAYLIVRA.</font></div>
    <div><br>
    </div>
    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Risks Associated with our Businesses as a Whole</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">We have incurred losses, and our business will suffer if we fail to consistently achieve profitability in the future.*</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Because drug discovery and development requires substantial lead-time and money prior to commercialization, our expenses
        have generally exceeded our revenue since we were founded in January 1989. As of March 31, 2019, we had an accumulated deficit of approximately $0.9 billion and stockholders&#8217; equity of approximately $1.4 billion. Most of our historical losses
        resulted from costs incurred in connection with our research and development programs and from selling, general and administrative costs associated with our operations. Most of our income has come from collaborative arrangements, including
        commercial revenue from royalties and R&amp;D revenue, with additional income from research grants and the sale or licensing of our patents, as well as interest income. If we do not continue to earn substantial revenue, we may incur additional
        operating losses in the future. We may not successfully develop any additional products or achieve or sustain future profitability.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">39</font></div>
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    </div>
    <div><br>
    </div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Our ability to use our net operating loss carryovers and certain other tax attributes may be limited.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 that provision, we can carryforward our NOLs to offset our future taxable income, if any, until such NOLs are used or expire. The same is true of other unused tax attributes,
        such as tax credits.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the Tax Cut and Jobs Act of 2017, or the Tax Act, federal net operating losses incurred in 2018 and in future years
        may be carried forward indefinitely, but the deductibility of such federal net operating losses is limited.&#160;It is uncertain if and to what extent various states will conform to the newly enacted federal tax law.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In addition, under Section 382 of the Internal Revenue Code of 1986, as amended, and corresponding provisions of state
        law, if a corporation undergoes an &#8220;ownership change,&#8221; which is generally defined as a greater than 50 percent change, by value, in its equity ownership over a three-year period, the corporation&#8217;s ability to use its pre-change net operating loss
        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 net operating loss carryforwards or other tax attributes is materially limited, it would harm our future operating results by effectively increasing our future tax obligations.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Since corporate partnering is a significant part of our strategy to fund the development 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our corporate partners are developing and/or funding many of the medicines in our development pipeline. If any of these
        pharmaceutical companies stops developing and/or funding these medicines, our business could suffer and we may not have, or be willing to dedicate, the resources available to develop these medicines on our own.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our collaborators can terminate their relationships with us under certain circumstances, many of which are outside of our
        control. For example, as part of a reprioritization of its pipeline and strategic review of its rare disease business, GSK declined its option on TEGSEDI and IONIS-FB-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In addition to receiving funding, we enter into collaborative arrangements with third parties to:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z79135b2fc01d4922b03bd32acf7d18ab" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">conduct clinical studies;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z01e9d105aa6d4bce9dee35d5c8dabc8b" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">seek and obtain marketing authorization; and</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z0f19e7b7d6544806b8b5cc8c407cd186" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">manufacture, market and sell our medicines.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Once we have secured a collaborative arrangement to further develop and commercialize one of our drug development
        programs, such as our collaborations with AstraZeneca, Bayer, Biogen, GSK, Janssen, Novartis and Roche, these collaborations may not continue or result in commercialized medicines, or may not progress as quickly as we first anticipated.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, a collaborator such as AstraZeneca, Bayer, Biogen, GSK, Janssen, Novartis or Roche, could determine that it
        is in its financial interest to:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z7c9537a44c3343c7930bc4f1763068a3" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">pursue alternative technologies or develop alternative products that may be competitive with the medicine that is part of the collaboration with us;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zdaf8f43eadbe4aec8130f386bc40b49b" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">pursue higher-priority programs or change the focus of its own development programs; or</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zf8c4b9a643b3447c9f3c7954769a3d31" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">choose to devote fewer resources to our medicines than it does for its own medicines.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If any of these occur, it could affect our partner&#8217;s commitment to the collaboration with us and could delay or otherwise
        negatively affect the commercialization of our medicines, including SPINRAZA.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If we do not progress in our programs as anticipated, the price of our securities could decrease.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 the clinic, when we anticipate completing a clinical study, or when we anticipate filing an application for, or obtaining, marketing authorization. We base our estimates on present facts and
        a variety of assumptions. Many underlying assumptions are outside of our control. If we do not achieve milestones in accordance with our or our investors&#8217; expectations, including milestones related to SPINRAZA, TEGSEDI and WAYLIVRA, the price of
        our securities could decrease.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">40</font></div>
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    </div>
    <div><br>
    </div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If we cannot protect our patents or our other proprietary rights, others may compete more effectively against us.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our success depends to a significant degree upon whether we can continue to develop and secure 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. 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Intellectual property litigation could be expensive and prevent us from pursuing our programs.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From time to time we have to defend our intellectual property rights. If we are involved in an intellectual property
        dispute, we sometimes need to litigate to defend our rights or assert them against others. Disputes can involve arbitration, litigation or proceedings declared by the U.S. Patent and Trademark Office or the International Trade Commission or foreign
        patent authorities. Intellectual property litigation can be extremely expensive, and this expense, as well as the consequences should we not prevail, could seriously harm our business.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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.</font></div>
    <div><br>
    </div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If we fail to obtain timely funding, we may need to curtail or abandon some of our programs.*</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Many of our medicines are undergoing clinical studies or are in the early stages of research and development. Most of our
        drug programs will require significant additional research, development, preclinical and/or clinical testing, marketing authorization and/or commitment of significant additional resources prior to their successful commercialization. As of March 31,
        2019, we had cash, cash equivalents and short-term investments equal to approximately $2.3 billion. If we do not meet our goals to successfully commercialize our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, or to license our medicines and
        proprietary technologies, we will need additional funding in the future. Our future capital requirements will depend on many factors, such as the following:</font></div>
    <div><br>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z01ae6d40fb304012898e5d1db57b8402" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">successful commercialization for SPINRAZA, TEGSEDI and WAYLIVRA;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z66743110243a4c6aa56b19ea6d741e4a" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">additional marketing approvals for WAYLIVRA and TEGSEDI;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z888e714d41684bbc80157ad32f2bdcab" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the profile and launch timing of our medicines, including TEGSEDI and WAYLIVRA;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="ze245ee71b2984087b7c0ebebbd5219f3" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">changes in existing collaborative relationships and our ability to establish and maintain additional collaborative arrangements;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="ze07a1664888f47ee983412a93e344307" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">continued scientific progress in our research, drug discovery and development programs;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z00baca3db8cc42f2b37697fac69ca08a" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the size of our programs and progress with preclinical and clinical studies;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z5cd9b319c4604dca87bb81198c9a46b6" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the time and costs involved in obtaining marketing authorizations; and</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z0bb2b06c542047c689ba5d135c124be8" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">competing technological and market developments, including the introduction by others of new therapies that address our markets.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If we need additional funds, we may need to raise them through public or private financing. Additional financing may not
        be available at all or on acceptable terms. If we raise additional funds by issuing equity securities, the shares of existing stockholders will be diluted and the price, as well as the price of our other securities, may decline. If adequate funds
        are not available or not available on acceptable terms, we may have to cut back on one or more of our research, drug discovery or development programs. Alternatively, we may obtain funds through arrangements with collaborative partners or others,
        which could require us to give up rights to certain of our technologies or medicines.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If our planned management transition is not successful our business could suffer.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2020, Dr. Crooke, our founder and Chief Executive Officer, plans to transition from Chief Executive Officer to
        Executive Chairman of our Board of Directors. As Executive Chairman, Dr. Crooke will continue to be responsible for the activities of the board and will remain active in the company, providing strategic advice and continuing to participate in the
        scientific activities. Our board has selected Dr. Monia, who has been our Chief Operating Officer for the last year and a member of our team since our founding nearly 30 years ago, to serve as our Chief Executive Officer starting in January 2020.&#160;
        If this transition is not successful, our business could suffer.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are dependent on the principal members of our management and scientific staff. We do not have employment agreements
        with any of our executive officers that would prevent them from leaving us. The loss of our management and key scientific employees might slow the achievement of important research and development goals. It is also critical to our success that we
        recruit and retain qualified scientific personnel to perform research and development work. We may not be able to attract and retain skilled and experienced scientific personnel on acceptable terms because of intense competition for experienced
        scientists among many pharmaceutical and health care companies, universities and non-profit research institutions. In addition, failure to succeed in clinical studies may make it more challenging to recruit and retain qualified scientific
        personnel.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">41</font></div>
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    </div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If the price of our securities continues to be highly volatile, this could make it harder for you to liquidate your
        investment and could increase your risk of suffering a loss.*</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 March 31, 2019, the market price of our common stock ranged from
        $39.07 to $81.59 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, governmental regulation, marketing authorization, changes in payors&#8217; reimbursement policies, developments in patent or other proprietary rights, public concern regarding the safety of our medicines
        and general market conditions.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our business exposes us to potential product liability risks that are inherent in the testing, manufacturing, marketing
        and sale of therapeutic products, including potential product liability claims related to SPINRAZA, TEGSEDI and WAYLIVRA. 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 drug products, 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z218cd347c6c749a597ce9eef79052c58" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">interruption of our research, development and manufacturing efforts;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zf4b5a9768fdd4eb89bf557fd19c16fa7" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">injury to our employees and others;</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z3c8ab11bf88e4880b0dd3814a4063bf8" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">environmental damage resulting in costly clean up; and</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zc96f78b4a38d4a21a051a5116c083f67" class="DSPFListTable">

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

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In such an event, we may be held liable for any resulting damages, and any liability could exceed our resources. Although
        we carry insurance in amounts and types that we consider commercially reasonable, we do not have insurance coverage for losses relating to an interruption of our research, development or manufacturing efforts caused by contamination, and the
        coverage or coverage limits of our insurance policies may not be adequate. If our losses exceed our insurance coverage, our financial condition would be affected.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">If a natural or man-made disaster strikes our research, development or manufacturing facilities or otherwise affects our
        business, it could delay our progress developing and commercializing our medicines.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We manufacture our research and clinical supplies in a manufacturing facility located in Carlsbad, California. We
        manufacture the finished drug product for TEGSEDI and WAYLIVRA at third-party contract manufacturers. The facilities and the equipment we and our contract manufacturers use to research, develop and manufacture our medicines would be costly to
        replace and could require substantial lead time to repair or replace. Our facilities or our contract manufacturers may be harmed by natural or man-made disasters, including, without limitation, earthquakes, floods, fires and acts of terrorism; and
        if our facilities are affected by a disaster, our development and commercialization efforts would be delayed. Although we possess insurance for damage to our property and the disruption of our business from casualties, 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Provisions in our certificate of incorporation, other agreements and Delaware law may prevent stockholders from receiving
        a premium for their shares.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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&#160;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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our certificate of incorporation also requires that any action required or permitted to be taken by our stockholders must
        be taken at a duly called annual or special meeting of stockholders and may not be taken by written consent. In addition, only our board of directors, chairman of the board or chief executive officer can call special meetings of our stockholders.
        We have in the past, and may in the future, implement a stockholders&#8217; rights plan, also called a poison pill, which could make it uneconomical for a third party to acquire our company on a hostile basis. In addition, our board of directors has the
        authority to fix the rights and preferences of, and issue shares of preferred stock, which may have the effect of delaying or preventing a change in control of our company without action by our stockholders.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">42</font></div>
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    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Future sales of our common stock in the public market could adversely affect the trading price of our securities.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font 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 10.3 million shares of our common stock upon conversion of our convertible senior notes. The addition of any of these shares into the public
        market may have an adverse effect on the price of our securities.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Each year we are required to evaluate our internal controls systems in order to allow management to report on and our
        Independent Registered Public Accounting Firm to attest to, our internal controls as required by Section 404 of the Sarbanes-Oxley Act. As a result, we continue to incur additional expenses and divert our management&#8217;s time to comply with these
        regulations. In addition, if we cannot continue to comply with the requirements of Section 404 in a timely manner, we might be subject to sanctions or investigation by regulatory authorities, such as the SEC, the Public Company Accounting Oversight
        Board, or PCAOB, or The Nasdaq Global Select Market. Any such action could adversely affect our financial results and the market price of our common stock.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The SEC and other regulators have continued to adopt new rules and regulations and make additional changes to existing
        regulations that require our compliance. On July 21, 2010, the Dodd-Frank Wall Street Reform and Protection Act, or the Dodd-Frank Act, was enacted. There are significant corporate governance and executive compensation-related provisions in the
        Dodd-Frank Act that require the SEC to adopt, or where the SEC has adopted, additional rules and regulations in these areas such as &#8220;say on pay&#8221; and proxy access. Stockholder activism, the current political environment and the current high level of
        government intervention and regulatory reform may lead to substantial new regulations and disclosure obligations, which may lead to additional compliance costs and impact the manner in which we operate our business.</font></div>
    <div><br>
    </div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Changes in tax laws, regulations and treaties could affect our future taxable income.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">A change in tax laws, treaties or regulations, or their interpretation, of any country in which we operate could
        materially affect us. For example, the Tax Act represented a substantial change to tax laws in the U.S. and although it did not have a material impact on our financial statements any future changes or interpretation to this or any other tax laws
        could have a material effect on our business.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">We could be subject to additional tax liabilities.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are subject to U.S. federal, state, local and sales taxes in the U.S. and foreign income taxes, withholding taxes and
        transaction taxes in foreign jurisdictions. Significant judgment is required in evaluating our tax positions and our worldwide provision for taxes. During the ordinary course of business, there are many activities and transactions for which the
        ultimate tax determination is uncertain. In addition, our tax obligations and effective tax rates could be adversely affected by changes in the relevant tax, accounting and other laws, regulations, principles and interpretations, including those
        relating to income tax nexus, by recognizing tax losses or lower than anticipated earnings in jurisdictions where we have lower statutory rates and higher than anticipated earnings in jurisdictions where we have higher statutory rates, by changes
        in foreign currency exchange rates, or by changes in the valuation of our deferred tax assets and liabilities. We may be audited in various jurisdictions, and such jurisdictions may assess additional taxes, sales taxes and value-added taxes against
        us. Although we believe our tax estimates are reasonable, the final determination of any tax audits or litigation could be materially different from our historical tax provisions and accruals, which could have a material adverse effect on our
        operating results or cash flows in the period for which a determination is made.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Negative conditions in the global credit markets and financial services and other industries may adversely affect our
        business.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The global credit markets, the financial services industry, the U.S. capital markets, and the U.S. economy as a whole have
        in the past experienced periods of substantial turmoil and uncertainty characterized by unprecedented intervention by the U.S. federal government and the failure, bankruptcy, or sale of various financial and other institutions. It is possible that
        a crisis in the global credit markets, the U.S. capital markets, the financial services industry or the U.S. economy may adversely affect our business, vendors and prospects, as well as our liquidity and financial condition. More specifically, our
        insurance carriers and insurance policies covering all aspects of our business may become financially unstable or may not be sufficient to cover any or all of our losses and may not continue to be available to us on acceptable terms, or at all.</font></div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">43</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">We are dependent on information technology systems, infrastructure and data, which exposes us to data security risks.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are dependent upon our own or third-party information technology systems, infrastructure and data, including mobile
        technologies, to operate our business.&#160;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.&#160;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.&#160;Cyber-attacks are increasing in their frequency, sophistication and intensity. 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.&#160;Our business partners face similar risks and any security breach of their systems could adversely affect our security posture.&#160;A security breach or privacy
        violation that leads to disclosure or modification of or prevents access to patient information, including personally identifiable information or protected health information, could harm our reputation, compel us to comply with federal and/or state
        breach notification laws and foreign law equivalents, subject us to mandatory 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/or 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.&#160;While we have invested, and continue to invest, in the protection of our data and information technology infrastructure, there can be no
        assurance that our efforts will prevent service interruptions, or identify breaches in our systems, that could adversely affect our business and operations and/or result in the loss of critical or sensitive information, which could result in
        financial, legal, business or reputational harm to us.&#160;In addition, our liability insurance may not be sufficient in type or amount to cover us against claims related to security breaches, cyber-attacks and other related breaches.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:28f26999-bee2-48f4-b34f-cd8573989c5c">
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="za87ba0c8dbfb4635825227d819713ac1" class="DSPFListTable">

            <tr>
              <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 2.</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Not applicable.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:c25f439c-e4a7-474b-8dec-41d56487749d">
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z81b8939472eb48d9b4d97b06835c5fc5" class="DSPFListTable">

            <tr>
              <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 3.</td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">DEFAULT UPON SENIOR SECURITIES</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Not applicable.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:13c71252-1c2d-489c-835a-8e8350ef751d">
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zcabb36e71821470aa18461c132a347d5" class="DSPFListTable">

            <tr>
              <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 4.</td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">MINE SAFETY DISCLOSURES</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Not applicable.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:4d4003f5-836a-49c6-9355-0766a48135b5">
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z395910a8e0cd4aecbb83268c4d16612e" class="DSPFListTable">

            <tr>
              <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 5.</td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">OTHER INFORMATION</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Not applicable.</font></div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:355aa042-4db7-41fe-8f4c-0e7fb80020fc">
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z71420e8c7cf34c99a834a1354aedce92" class="DSPFListTable">

            <tr>
              <td style="width: 72pt; vertical-align: top; align: right; 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><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">EXHIBITS</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: left;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z064a6c1997ff41eeaa4c072e9214c1ad" class="DSPFListTable">

            <tr>
              <td style="width: 36pt;"></td>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a.</font></td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Exhibits</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">44</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zacf79a728df64f3589ee64e3d2a3d414">

        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: #FFFFFF; border-bottom: #000000 2px solid;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Exhibit Number</font></div>
          </td>
          <td style="width: 2%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 90.27%; vertical-align: bottom; background-color: #FFFFFF; border-bottom: #000000 2px solid;">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Description of Document</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 2%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><a href="http://www.sec.gov/Archives/edgar/data/874015/000114036119005627/ex10_1.htm">10.1</a></font></div>
          </td>
          <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Amended and Restated Strategic Advisory Services Agreement by and between the Registrant and B. Lynne Parshall, dated March 22,
                2019.&#160; &#8211; Filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed March 26, 2019 and incorporated herein by reference.</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 2%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><a href="http://www.sec.gov/Archives/edgar/data/874015/000114036119005627/ex10_2.htm">10.2</a></font></div>
          </td>
          <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Registrant&#8217;s Amended and Restated 2000 Employee Stock Purchase Plan. &#8211; Filed as an exhibit to the Registrant&#8217;s Current Report on Form
                8-K filed March 26, 2019 and incorporated herein by reference.</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 2%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: rgb(204, 238, 255); border-bottom: 2px solid black;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><a href="ex31_1.htm"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">31.1</font></a></font></div>
          </td>
          <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Certification by Chief Executive Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as
                amended.</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 2%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><a href="ex31_2.htm">31.2</a></font></div>
          </td>
          <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Certification by Chief Financial Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as
                amended.</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 2%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><a href="ex32_1.htm">32.1</a>*</font></div>
          </td>
          <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Certification Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 2%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 7.73%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">101</font></div>
          </td>
          <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 90.27%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following financial statements from the Ionis Pharmaceuticals, Inc. Quarterly Report on Form 10-Q for the quarter ended March 31,
                2019, formatted in Extensive Business Reporting Language (XBRL): (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' equity, (v) condensed consolidated statements of cash flows and (vi) notes to condensed consolidated financial statements (detail tagged).</font></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="zf47d16310ac841fcbd08406388b824a9" class="DSPFListTable">

            <tr>
              <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</font></td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">This certification is deemed not filed for purposes of Section&#160;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.</font></font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
  </div>
  <div id="TRGRSegment:438d4248-9723-4818-a871-14f86b890434">
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">45</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <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-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">SIGNATURES</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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.</font></div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;" id="z47d65059d4094432b3e89cbd02f0d04d">

        <tr>
          <td style="width: 27.63%; vertical-align: bottom; border-bottom: #000000 2px solid;">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Signatures</font></div>
          </td>
          <td style="width: 2.17%; vertical-align: bottom;">&#160;</td>
          <td style="width: 50.43%; vertical-align: bottom; border-bottom: #000000 2px solid;">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Title</font></div>
          </td>
          <td style="width: 2.12%; vertical-align: bottom;">&#160;</td>
          <td style="width: 17.66%; vertical-align: bottom; border-bottom: #000000 2px solid;">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Date</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 27.63%; vertical-align: top;">&#160;</td>
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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">/s/ STANLEY T. CROOKE</font></div>
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          <td style="width: 2.17%; vertical-align: bottom;" rowspan="2">&#160;</td>
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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Stanley T. Crooke, M.D., Ph.D.</font></div>
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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(Principal executive officer)</font></div>
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          <td style="width: 17.66%; vertical-align: bottom;">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">May 9, 2019</font></div>
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          <td style="width: 27.63%; vertical-align: top;">&#160;</td>
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          <td style="width: 27.63%; vertical-align: top; border-bottom: #000000 2px solid;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">/s/ ELIZABETH L. HOUGEN</font></div>
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          <td style="width: 2.17%; vertical-align: bottom;" rowspan="2">&#160;</td>
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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Senior Vice President, Finance and Chief Financial Officer</font></div>
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          <td style="width: 2.12%; vertical-align: bottom;" rowspan="2">&#160;</td>
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        <tr>
          <td style="width: 27.63%; vertical-align: top;">
            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Elizabeth L. Hougen</font></div>
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            <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(Principal financial and accounting officer)</font></div>
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          <td style="width: 17.66%; vertical-align: bottom;">
            <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">May 9, 2019</font></div>
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        </tr>

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  <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">46</font></div>
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<DOCUMENT>
<TYPE>EX-31.1
<SEQUENCE>2
<FILENAME>ex31_1.htm
<DESCRIPTION>EXHIBIT 31.1
<TEXT>
<html><head>
    <title>&#160;</title>
    <!-- Licensed to: Ionis
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  </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'; font-size: 10pt;">EXHIBIT 31.1</div><div><br></div><div style="text-align: center;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">CERTIFICATION</font></div><div><br></div><div style="text-align: justify;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">I, Stanley T. Crooke, certify that:</font></div><div><br></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z1ee91f8442a148b0af669ef2054d909b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">1.</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-family: 'Times New Roman'; font-size: 10pt;">I have reviewed this Quarterly Report on Form 10-Q of Ionis Pharmaceuticals, Inc.;</font></div></td></tr></table></div></div><div><br></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd67df1fd70f344eda6b8d418fc365576" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; 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vertical-align: top; text-align: justify;"><div><font style="font-family: 'Times New Roman'; font-size: 10pt;">Based on my knowledge, the condensed consolidated financial statements, and other financial information included in this quarterly report, fairly present in all material respects the financial condition, condensed consolidated results of operations and condensed consolidated cash flows of the registrant as of, and for, the periods presented in this quarterly report;</font></div></td></tr></table></div></div><div><br></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zced9fabfd1314bb78036a8ce0c907615" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">4.</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-family: 'Times New Roman'; 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CROOKE</font></div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">&#160;</font></div></td></tr><tr><td style="width: 27.75%; vertical-align: top;"><div style="text-align: left;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">Stanley T. Crooke, M.D., Ph.D.</font></div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">&#160;</font></div></td></tr><tr><td style="width: 27.75%; vertical-align: top;"><div style="text-align: left;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">Chief Executive Officer</font></div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">&#160;</font></div></td></tr></table><div><br></div></div></body></html>
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<DOCUMENT>
<TYPE>EX-31.2
<SEQUENCE>3
<FILENAME>ex31_2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
<html><head>
    <title>&#160;</title>
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  </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'; font-size: 10pt;">EXHIBIT 31.2</div><div><br></div><div style="text-align: center;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">CERTIFICATION</font></div><div><br></div><div style="text-align: justify;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">I, Elizabeth L. Hougen, certify that:</font></div><div><br></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4b3f85c431e14713829e0a52b82e1865" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">1.</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-family: 'Times New Roman'; font-size: 10pt;">I have reviewed this Quarterly Report on Form 10-Q of Ionis Pharmaceuticals, Inc.;</font></div></td></tr></table></div></div><div><br></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zec68b63c8cb343f0b6910e72622ac9d9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; 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  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:3d169df3-22e7-43e5-8644-a48762b313e4"><div style="text-align: right; font-family: 'Times New Roman'; font-size: 10pt;">Exhibit 32.1</div><div><br></div><div style="text-align: center;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">CERTIFICATION</font></div><div><br></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-family: 'Times New Roman'; font-size: 10pt;">Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, Stanley T. Crooke, the Chief Executive Officer of Ionis Pharmaceuticals, Inc., (the &#8220;Company&#8221;), and Elizabeth L. 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We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 March 31, 2019:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;One year or less&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;74%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;After one year but within two years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;21%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;After two years but within three years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;100%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As illustrated above, at March 31, 2019, 95 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="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;All of our available-for-sale 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;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;At March 31, 2019, we had an ownership interest of less than 20 percent in four private companies and two public companies with which we conduct business. The privately-held companies are Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd. The publicly-traded companies are ProQR and ATL.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;/font&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%;"&gt;&lt;tr&gt;&lt;td rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;/td&gt;&lt;td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" rowspan="1" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" rowspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Gross Unrealized&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" rowspan="1" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" rowspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" rowspan="1" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/font&gt;(1)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" rowspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Gains&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Losses&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" rowspan="1" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Estimated Fair Value&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" rowspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Available-for-sale securities:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Corporate debt securities (2)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;869,483&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;326&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(531&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;869,278&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by U.S. government agencies&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;124,744&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;71&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(15&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;124,800&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;328,340&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;110&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(12&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;328,438&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;63,366&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;10&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(203&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;63,173&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Other municipal debt securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,931&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,932&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: 13.5pt; margin-left: 4.5pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total securities with a maturity of one year or less&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,388,864&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,388,621&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Corporate debt securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;360,976&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,236&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by U.S. government agencies&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;120,341&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;279&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(112&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;120,508&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by the U.S. Treasury&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; 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width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(22&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;33,559&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;15,615&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; 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vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;15,490&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: 13.5pt; margin-left: 4.5pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total securities with a maturity of more than one year&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;530,501&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; 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vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;531,433&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total available-for-sale securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,919,365&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; 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font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1,356&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,920,054&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Equity securities:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; 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font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;968&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total available-for-sale and equity securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,920,577&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; 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vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" rowspan="1" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" rowspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;December 31, 2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" rowspan="1" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; 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font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;168,738&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;15&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(77&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;244,578&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; 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font-family: 'Times New Roman', Times, serif;"&gt;(2,362&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,431,599&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Corporate debt securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;299,018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;194&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1,286&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;297,926&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by U.S. government agencies&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;107,789&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;194&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(109&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;107,874&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by the U.S. Treasury&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;15,600&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(24&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;15,576&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;16,980&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(287&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;16,693&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total securities with a maturity of more than one year&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;439,387&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;388&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1,706&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;438,069&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total available-for-sale securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,873,317&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;419&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(4,068&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,869,668&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Equity securities:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total equity securities included in other current assets (3)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,212&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;137&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,349&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total available-for-sale and equity securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,874,529&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;556&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(4,068&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,871,017&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our available-for-sale securities are held at amortized cost.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(2)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Includes investments classified as cash equivalents on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(3)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize our equity securities at 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 on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 March 31, 2019. 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. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&amp;#8217; amortized cost basis at maturity.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table border="0" cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 30%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Less than 12 Months of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Temporary Impairment&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;More than 12 Months of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 30%; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by U.S. government agencies&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; 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  <!--Collaborative Arrangement Disclosure [Text Block]-->
  <us-gaap:CollaborativeArrangementDisclosureTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;7.&amp;#160; Collaborative Arrangements and Licensing Agreements&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Below, we have included our collaborations with substantive changes during the first three months of 2019 from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2018.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Strategic Partnership&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;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;Biogen&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&amp;#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. In&lt;/font&gt; December 2017, we entered into a collaboration with Biogen to identify &lt;font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;new antisense medicines for the treatment of SMA&lt;/font&gt;. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Additionally, we and Biogen are currently developing six other medicines to treat neurodegenerative diseases under these collaborations, including tofersen (formerly IONIS-SOD1&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;) for ALS patients with SOD1 mutations, or SOD1-ALS, which Biogen moved into a Phase 3 study in the first quarter of 2019, IONIS-MAPT&lt;/font&gt;&lt;sub&gt;Rx &lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for Alzheimer&amp;#8217;s disease&lt;/font&gt;&lt;sub&gt;,&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; IONIS-C9&lt;/font&gt;&lt;sub&gt;Rx &lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for ALS patients with C9ORF72 mutations, and IONIS-BIIB6&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, IONIS-BIIB7&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and IONIS-BIIB8&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to treat undisclosed neurodegenerative diseases. In addition to these medicines, we and Biogen are evaluating numerous additional targets to develop medicines to treat neurological diseases. In April 2018, we entered into a new strategic collaboration for the treatment of neurological diseases with Biogen. From inception through March 2019, we have received over $2.1 billion from our Biogen collaborations, including $1 billion we received from Biogen in the second quarter of 2018 for our 2018 strategic neurology collaboration.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt; 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;SPINRAZA royalties (commercial revenue)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;59.7&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;41.1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;R&amp;amp;D revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;24.5&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;10.8&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total revenue from our relationship with Biogen&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;84.2&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;51.9&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Percentage of total revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;28&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;36&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the first quarter of 2019, we did not have any changes to our performance obligations or the timing in which we expect to recognize revenue under our Biogen collaborations.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In April 2019, we achieved a $7.5 million milestone payment from Biogen, when we advanced a new target for an unidentified neurological disease&lt;sub&gt;&amp;#160;&lt;/sub&gt;under the 2018 strategic neurology collaboration. We will achieve the next payment of up to $10 million if Biogen designates a target under our 2018 strategic neurology collaboration.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our condensed consolidated balance sheet at March 31, 2019 and &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;December 31, 2018 &lt;/font&gt;included deferred revenue of $556.4 million and $580.9 million, respectively, related to our relationship with Biogen.&lt;/font&gt;&lt;/div&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; font-weight: bold;"&gt;Research, Development and Commercialization Partners&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;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;Roche&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have two collaborations with Roche, one to develop treatments for Huntington's disease, or HD, and one to &lt;/font&gt;&lt;font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;develop IONIS-FB-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;for the treatment of complement-mediated diseases. In December 2017, upon completion of the Phase 1/2 study of IONIS-HTT&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, Roche exercised its option to license IONIS-HTT&lt;/font&gt;&lt;sub&gt;Rx &lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;and is now responsible for the global development, regulatory and commercialization activities for IONIS-HTT&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. In October 2018, we entered into a collaboration agreement with Roche to&lt;/font&gt;&lt;font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; develop IONIS-FB-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;for the treatment of complement-mediated diseases. The first indication we plan to pursue is the treatment of patients with geographic atrophy, or GA, the advanced stage of dry age-related macular degeneration, or AMD. We are responsible for conducting a Phase 2 study in patients with dry AMD. In addition, we plan to evaluate the medicine for a severe and rare renal indication.&amp;#160;&lt;/font&gt;Roche&lt;font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;has the option to license IONIS-FB-L&lt;/font&gt;&lt;sub&gt;&lt;font style="background-color: #FBFBFB;"&gt;Rx&lt;/font&gt;&lt;/sub&gt;&lt;font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;at the completion of these studies. Upon licensing,&amp;#160;&lt;/font&gt;Roche &lt;font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;will be responsible for all further global development, regulatory and commercialization activities and costs.&lt;/font&gt;&amp;#160;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through March 2019, we have received over $220 million from our Roche collaborations, including $35 million in &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;milestone payments we earned in the first quarter of 2019 when Roche dosed the first patient in a Phase 3 study for IONIS-HTT&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We will achieve the next payment of $15 million if Roche advances IONIS-HTT&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt; 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;R&amp;amp;D revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;41.2&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.0&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Percentage of total revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;14&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 revenue in the first quarter of 2019, included $35 million of milestone payments we earned when Roche dosed the first patient in the Phase 3 study of IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt;. We recognized these milestone payments in full in the first quarter of 2019 because we do not have any performance obligations related to these milestone payments as Roche is conducting the Phase 3 study of IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;During the first quarter of 2019, we did not have any changes to our performance obligations or the timing in which we expect to recognize revenue under our Roche collaborations.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our condensed consolidated balance sheet at March 31, 2019 and &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;December 31, 2018 &lt;/font&gt;included deferred revenue of $67.5 million and $72.6 million, respectively, related to our relationship with Roche.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;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;Akcea Collaboration&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following collaboration agreement relates to Akcea, our majority owned affiliate. Our consolidated results include all the revenue earned and cash received under this collaboration agreement. We reflect the noncontrolling interest attributable to other owners of Akcea&amp;#8217;s common stock in a separate line on the statement of operations and a separate line within stockholders&amp;#8217; equity in our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Novartis&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In January 2017, we and Akcea initiated a collaboration with Novartis to develop and commercialize AKCEA-APO(a)-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and AKCEA-APOCIII-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/font&gt;&lt;sub&gt;&amp;#160;&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Under the collaboration agreement, Novartis has an exclusive option to further develop and commercialize AKCEA-APO(a)-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and AKCEA-APOCIII-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Akcea is responsible for completing a Phase 2 program, conducting an end-of-Phase 2 meeting with the FDA and providing initial quantities of API for each medicine. If Novartis exercises an option for either of these medicines, Novartis will be responsible for all further global development, regulatory and co-commercialization activities and costs for such medicine. &lt;/font&gt;In the first quarter of 2019, Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;. Novartis is responsible for conducting and funding all future development, regulatory and commercialization activities for AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;, including a global pivotal cardiovascular outcomes study, for which planning and initiation activities are underway. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through March 2019, we have received over $330 million from our Novartis collaboration, including $150 million we earned from Novartis in the first quarter of 2019 for the license of AKCEA-APO(a)-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;. Akcea paid us $75 million as a sublicense fee in 2.8 million shares of Akcea common stock.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We identified a new performance obligation when we granted Novartis the license of AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; in the first quarter of 2019 because the license is distinct from our other performance obligations. We recognized the $150 million license fee for AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; as revenue at that time because Novartis had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Novartis.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea is responsible for the development activities under this collaboration. As such, Akcea is recognizing the associated revenue in its statement of operations, and we reflect all of Akcea&amp;#8217;s revenue in our consolidated results. Akcea pays us sublicense fees for payments that it receives under the collaboration and we recognize those fees as revenue in our Ionis Core operating segment results and Akcea recognizes the fees as R&amp;amp;D expense. In our consolidated results, we eliminate this sublicense revenue and expense. Any cash Akcea receives is included in our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt; 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;R&amp;amp;D revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;157.1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;17.1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Percentage of total revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;53&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;12&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the first quarter of 2019, we did not have any changes to our performance obligations, except as noted above, or the timing in which we expect to recognize revenue under our Novartis collaboration.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our condensed consolidated balance sheet at March 31, 2019 and December 31, 2018 included deferred revenue of $23.3 million and $28.8 million, respectively, related to our relationship with Novartis.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:CollaborativeArrangementDisclosureTextBlock>
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  <us-gaap:ConsolidationPolicyTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In the condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals,&amp;#160;Inc. and the consolidated results of our majority owned affiliate,&amp;#160;Akcea Therapeutics, Inc. and its wholly owned subsidiaries. We formed Akcea in December 2014. &lt;/font&gt;In July 2017, Akcea completed an &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;initial public offering, or IPO,&lt;/font&gt; and therefore, beginning in July 2017, we no longer owned 100 percent of Akcea. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;, increasing our ownership to approximately 76 percent at March 31, 2019. We reflected the increase in our ownership in these financial statements. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Refer to the section titled &amp;#8220;Noncontrolling Interest in Akcea&amp;#8221; in Note 2, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies,&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for further information related to our accounting for our investment in Akcea.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ConsolidationPolicyTextBlock>
  <!--Consolidation, Subsidiaries or Other Investments, Consolidated Entities, Policy [Policy Text Block]-->
  <us-gaap:ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Noncontrolling Interest in Akcea Therapeutics, Inc.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Prior to Akcea&amp;#8217;s IPO in July 2017, we owned 100 percent of Akcea. From the closing of Akcea&amp;#8217;s IPO in July 2017 through mid-April 2018, we owned approximately 68 percent&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;of Akcea. In the second, third and fourth quarters of 2018, we received additional shares of Akcea&amp;#8217;s stock related to our license of TEGSEDI and AKCEA-TTR-L&lt;sub&gt;Rx&lt;/sub&gt; to Akcea, increasing our ownership percentage to approximately 75 percent. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;, increasing our ownership to approximately 76 percent at March 31, 2019. We reflected this increase in our ownership percentage in these financial statements as an adjustment to noncontrolling interest. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The shares third parties own represent an interest in Akcea&amp;#8217;s equity that is not controlled by us. However, as we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our condensed consolidated financial statements. We reflect the noncontrolling interest attributable to other owners of Akcea&amp;#8217;s common stock in a separate line on the statement of operations and a separate line within stockholders&amp;#8217; equity in our condensed consolidated balance sheet. In addition, we record a noncontrolling interest adjustment to account for the stock options Akcea grants, which if exercised, will dilute our ownership in Akcea. This adjustment is a reclassification within stockholders&amp;#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy>
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  <!--Contract with Customer, Liability-Collaborative Arrangements and Licensing Agreements, Biogen [Member]-->
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  <!--Contract with Customer, Liability-Collaborative Arrangements and Licensing Agreements, Roche [Member]-->
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  <!--Contract with Customer, Liability-Collaborative Arrangements and Licensing Agreements, Roche [Member]-->
  <us-gaap:ContractWithCustomerLiability contextRef="c20181231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U002" decimals="-5">72600000</us-gaap:ContractWithCustomerLiability>
  <!--Contract with Customer, Liability-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
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  <!--Contract with Customer, Liability-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
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  <!--Contract with Customer, Asset, Net, Current-->
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  <!--Contract with Customer, Asset, Net, Current-->
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  <!--Contract with Customer, Liability, Current-->
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  <!--Contract with Customer, Liability, Current-->
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  <!--Convertible Debt, Noncurrent-->
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  <!--Cost of Goods and Services Sold-->
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  <!--Cost of Goods and Services Sold-->
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  <!--Cost of Sales, Policy [Policy Text Block]-->
  <us-gaap:CostOfSalesPolicyTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Products Sold&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our cost of products sold includes manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of TEGSEDI. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of products sold. Prior to obtaining regulatory approval in July 2018, we expensed a significant portion of the costs we incurred to produce the TEGSEDI supply we are using in the commercial launch as research and development expense. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We previously recognized $0.3 million of costs to produce TEGSEDI related to the TEGSEDI commercial revenue we recognized in the&lt;/font&gt; three months ended March 31, 2019.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:CostOfSalesPolicyTextBlock>
  <!--Costs and Expenses-->
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  <!--Costs and Expenses-->
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  <!--Costs and Expenses-Operating Segments [Member]-Akcea Therapeutics [Member]-->
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  <!--Costs and Expenses-Operating Segments [Member]-Ionis Core [Member]-->
  <us-gaap:CostsAndExpenses contextRef="c20190101to20190331_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3">114515000</us-gaap:CostsAndExpenses>
  <!--Costs and Expenses-Elimination of Intercompany Activity [Member]-->
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  <!--Costs and Expenses-Operating Segments [Member]-Akcea Therapeutics [Member]-->
  <us-gaap:CostsAndExpenses contextRef="c20190101to20190331_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3">137610000</us-gaap:CostsAndExpenses>
  <!--Costs and Expenses-Elimination of Intercompany Activity [Member]-->
  <us-gaap:CostsAndExpenses contextRef="c20190101to20190331_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3">-76446000</us-gaap:CostsAndExpenses>
  <!--Costs and Expenses-Operating Segments [Member]-Ionis Core [Member]-->
  <us-gaap:CostsAndExpenses contextRef="c20180101to20180331_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3">105544000</us-gaap:CostsAndExpenses>
  <!--Debt, Policy [Policy Text Block]-->
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  <!--Debt Instrument, Interest Rate, Stated Percentage-Convertible Senior Notes 1 Percent [Member]-->
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  <!--Depreciation-->
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  <!--Depreciation-->
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  <!--Basic net income (loss) per share (in dollars per share)-->
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  <!--Basic net income (loss) per share (in dollars per share)-->
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  <!--Basic net income (loss) per share (in dollars per share)-Common Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
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  <!--Basic net income (loss) per share (in dollars per share)-Akcea Therapeutics, Inc. [Member]-Common Stock [Member]-->
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  <!--Earnings Per Share, Policy [Policy Text Block]-->
  <us-gaap:EarningsPerSharePolicyTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div&gt;&lt;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 and diluted net income (loss) per share&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Basic net income (loss) per share&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The calculation of total net income (loss) attributable to our common stockholders for the three months ended March 31, 2019 and 2018 considered our net income for Ionis on a stand-alone basis plus our share of Akcea&amp;#8217;s net loss for the period. To calculate the portion of Akcea&amp;#8217;s net loss attributable to our ownership, we multiplied Akcea&amp;#8217;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our&amp;#160;total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 basic net income per share for the three months ended &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;March 31, 2019&lt;/font&gt;, was calculated as follows (in thousands, except per share amounts):&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three months ended March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Weighted&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Average Shares&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Owned in Akcea&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Net Income&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Per Share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Ionis&amp;#8217; Portion of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s Net Loss&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Common shares&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;68,582&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.35&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;23,846&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea&amp;#8217;s net income attributable to our ownership&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;23,846&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;63,697&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Net income available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;87,543&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Weighted average shares outstanding&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;138,582&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Basic net income per share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.63&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#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; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net loss per share for the three months ended &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;March 31, 2018&lt;/font&gt;, was calculated as follows (in thousands, except per share amounts):&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three months ended March 31, 2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Weighted&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Average Shares&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Owned in Akcea&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Net Loss&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Per Share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Ionis&amp;#8217; Portion of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s Net Loss&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Common shares&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;45,448&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(0.44&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(19,997&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(19,997&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;18,785&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Net loss available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1,212&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Weighted average shares outstanding&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;125,330&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Basic net loss per share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(0.01&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Dilutive net income (loss per share)&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For the three months ended March 31, 2019, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 diluted net income per share for the three months ended March 31, 2019 as follows (in thousands except per share amounts):&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three months ended March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Income&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Numerator)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Shares&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Denominator)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Per-Share&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Amount&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Net income available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Shares issuable upon exercise of stock options&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;38&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Income available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; 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text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;141,537&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.62&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#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; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three months ended March 31, 2019, the calculation excluded the 1 percent notes because the effect on diluted earnings per share was anti-dilutive.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For the three months ended March 31, 2018, 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. 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  <!--Effective Income Tax Rate Reconciliation, at Federal Statutory Income Tax Rate, Percent-->
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  <!--Effective Income Tax Rate Reconciliation, Percent-->
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  <us-gaap:FairValueDisclosuresTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;4.&amp;#160; Fair Value Measurements&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1, defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly-held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify the majority of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following tables present the major security types we held at March 31, 2019 and December 31, 2018 that we regularly measure and carry at fair value. At March 31, 2019 and December 31, 2018, &lt;/font&gt;our ProQR investment was &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;subject to trading restrictions that extend through the fourth quarter of 2019, as a result we&lt;/font&gt; included a lack of marketability discount in valuing this investment,&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;which is a Level 3 input.&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; The amount we owned in ProQR did not change from December 31, 2018 to March 31, 2019. The tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&amp;#8217; fair value (in thousands):&lt;/font&gt;&lt;/font&gt;&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;At&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Quoted Prices in&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Active Markets&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Level 1)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Significant Other&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Observable Inputs&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Level 2)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Significant Unobservable Inputs&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Level 3)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Cash equivalents (1)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Other municipal debt securities (3)&lt;/font&gt;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,932&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; 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(5)&lt;/font&gt;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;968&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; 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font-family: 'Times New Roman', Times, serif;"&gt;508,539&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,558,057&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;968&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;At&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;December 31, 2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; 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width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (3)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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(5)&lt;/font&gt;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,349&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,349&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,017,298&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;406,435&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,609,514&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,349&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#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;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Included in cash and cash equivalents on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(2) $27.1 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(3)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Included in short-term investments on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(4)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$15.0 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(5)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Included in other current assets on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(6)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$50.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(7)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$14.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Convertible Notes&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our 1 percent notes had a fair value of $928.4 million at March 31, 2019. 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;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:FairValueDisclosuresTextBlock>
  <!--Fair Value, Assets Measured on Recurring Basis [Table Text Block]-->
  <us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following tables present the major security types we held at March 31, 2019 and December 31, 2018 that we regularly measure and carry at fair value. At March 31, 2019 and December 31, 2018, &lt;/font&gt;our ProQR investment was &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;subject to trading restrictions that extend through the fourth quarter of 2019, as a result we&lt;/font&gt; included a lack of marketability discount in valuing this investment,&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;which is a Level 3 input.&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; The amount we owned in ProQR did not change from December 31, 2018 to March 31, 2019. The tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&amp;#8217; fair value (in thousands):&lt;/font&gt;&lt;/font&gt;&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;At&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Quoted Prices in&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Active Markets&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Level 1)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Significant Other&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Observable Inputs&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Level 2)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Significant Unobservable Inputs&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Level 3)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Cash equivalents (1)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;146,542&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;146,542&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Other municipal debt securities (3)&lt;/font&gt;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,932&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; 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vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;968&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#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" style="font-family: 'Times New Roman', Times, serif; 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text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;146,281&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;146,281&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Corporate debt securities (6)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,252,960&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; 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width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by the U.S. Treasury (7)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;260,154&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;260,154&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (3)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;79,942&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;79,942&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;/div&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Investment in ProQR Therapeutics N.V. (5)&lt;/font&gt;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,349&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,349&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,017,298&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;406,435&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,609,514&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,349&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#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;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Included in cash and cash equivalents on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(2) $27.1 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(3)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Included in short-term investments on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(4)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$15.0 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(5)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Included in other current assets on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(6)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$50.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(7)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$14.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock>
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  <us-gaap:FiniteLivedIntangibleAssetsNet contextRef="c20181231" unitRef="U002" decimals="-3">24032000</us-gaap:FiniteLivedIntangibleAssetsNet>
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  <us-gaap:FiniteLivedIntangibleAssetsNet contextRef="c20190331" unitRef="U002" decimals="-3">25220000</us-gaap:FiniteLivedIntangibleAssetsNet>
  <!--Impairment or Disposal of Long-Lived Assets, Including Intangible Assets, Policy [Policy Text Block]-->
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  <!--Income (Loss) from Continuing Operations before Equity Method Investments, Income Taxes, Noncontrolling Interest-->
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  <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments contextRef="c20190101to20190331" unitRef="U002" decimals="-3">121931000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments>
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  <us-gaap:IncomeTaxExpenseBenefit contextRef="c20190101to20190331" unitRef="U002" decimals="-3">31047000</us-gaap:IncomeTaxExpenseBenefit>
  <!--Income Tax Expense (Benefit)-->
  <us-gaap:IncomeTaxExpenseBenefit contextRef="c20180101to20180331" unitRef="U002" decimals="-3">15000</us-gaap:IncomeTaxExpenseBenefit>
  <!--Income Tax Disclosure [Text Block]-->
  <us-gaap:IncomeTaxDisclosureTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&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;6.&amp;#160; Income Taxes&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 24.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our effective tax rate may vary from the U.S. federal statutory tax rate due to the change in the mix of earnings in tax jurisdictions with different statutory rates, benefits related to tax credits, and the tax impact of non-deductible expenses and other permanent differences between income before income taxes and taxable income.&amp;#160; Our effective income tax rate of 25.5 percent for the three months ended March 31, 2019 differed from the U.S. federal statutory rate of 21 percent primarily due to state taxes, partially offset by the tax benefit related to estimated research &amp;amp; development and orphan drug credits and the excess tax benefit related to share-based compensation.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recorded income tax expense of $31 million for the three months ended March 31, 2019, compared to $15,000 &lt;/font&gt;for the same period in 2018. The increase in our income tax expense was primarily due to our expectation that we will generate U.S. federal and state taxable income in 2019. Our 2019 income tax expense has two components. The first component relates to federal income taxes. We expect to utilize our deferred tax assets to offset our U.S. federal taxable income. We are recording non-cash income tax expense as we utilize our federal deferred tax assets.&amp;#160;The other component of our income tax expense relates to the estimated cash taxes we will pay for our state income taxes. Although we are recording the expense for our state income taxes in 2019, we will not have to make the majority of the payment for this liability until the first quarter of 2020.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:IncomeTaxDisclosureTextBlock>
  <!--Income Tax, Policy [Policy Text Block]-->
  <us-gaap:IncomeTaxPolicyTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income Taxes&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act of 2017, or the Tax Act. The Tax Act created a new requirement on global intangible low-taxed income, or GILTI, earned by foreign subsidiaries for tax years beginning on or after January 1, 2018. The GILTI provisions require foreign subsidiary earnings in excess of an allowable return on the foreign subsidiary&amp;#8217;s assets to be included in our U.S. income tax return. Under U.S. GAAP, we are permitted to make an accounting policy election to either treat taxes due on future inclusions in U.S. taxable income related to GILTI as a current-period expense when incurred or to factor such amounts into our measurement of deferred taxes. We have made the election to account for GILTI as a component of current taxes incurred rather than as a component of deferred taxes.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:IncomeTaxPolicyTextBlock>
  <!--Increase (Decrease) in Contract with Customer, Liability-->
  <us-gaap:IncreaseDecreaseInContractWithCustomerLiability contextRef="c20190101to20190331" unitRef="U002" decimals="-3">-40353000</us-gaap:IncreaseDecreaseInContractWithCustomerLiability>
  <!--Increase (Decrease) in Contract with Customer, Liability-->
  <us-gaap:IncreaseDecreaseInContractWithCustomerLiability contextRef="c20180101to20180331" unitRef="U002" decimals="-3">-27788000</us-gaap:IncreaseDecreaseInContractWithCustomerLiability>
  <!--Increase (Decrease) in Contract with Customer, Asset-->
  <us-gaap:IncreaseDecreaseInContractWithCustomerAsset contextRef="c20190101to20190331" unitRef="U002" decimals="-3">-4908000</us-gaap:IncreaseDecreaseInContractWithCustomerAsset>
  <!--Increase (Decrease) in Contract with Customer, Asset-->
  <us-gaap:IncreaseDecreaseInContractWithCustomerAsset contextRef="c20180101to20180331" unitRef="U002" decimals="-3">-26097000</us-gaap:IncreaseDecreaseInContractWithCustomerAsset>
  <!--Increase (Decrease) in Accounts Payable-->
  <us-gaap:IncreaseDecreaseInAccountsPayable contextRef="c20180101to20180331" unitRef="U002" decimals="-3">-13144000</us-gaap:IncreaseDecreaseInAccountsPayable>
  <!--Increase (Decrease) in Accounts Payable-->
  <us-gaap:IncreaseDecreaseInAccountsPayable contextRef="c20190101to20190331" unitRef="U002" decimals="-3">-17191000</us-gaap:IncreaseDecreaseInAccountsPayable>
  <!--Increase (Decrease) in Inventories-->
  <us-gaap:IncreaseDecreaseInInventories contextRef="c20190101to20190331" unitRef="U002" decimals="-3">2475000</us-gaap:IncreaseDecreaseInInventories>
  <!--Increase (Decrease) in Inventories-->
  <us-gaap:IncreaseDecreaseInInventories contextRef="c20180101to20180331" unitRef="U002" decimals="-3">-922000</us-gaap:IncreaseDecreaseInInventories>
  <!--Increase (Decrease) in Other Operating Assets-->
  <us-gaap:IncreaseDecreaseInOtherOperatingAssets contextRef="c20190101to20190331" unitRef="U002" decimals="-3">-1802000</us-gaap:IncreaseDecreaseInOtherOperatingAssets>
  <!--Increase (Decrease) in Other Operating Assets-->
  <us-gaap:IncreaseDecreaseInOtherOperatingAssets contextRef="c20180101to20180331" unitRef="U002" decimals="-3">-11422000</us-gaap:IncreaseDecreaseInOtherOperatingAssets>
  <!--Increase (Decrease) in Other Employee-Related Liabilities-->
  <us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities contextRef="c20180101to20180331" unitRef="U002" decimals="-3">-12985000</us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities>
  <!--Increase (Decrease) in Other Employee-Related Liabilities-->
  <us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities contextRef="c20190101to20190331" unitRef="U002" decimals="-3">-13004000</us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities>
  <!--Shares issuable related to stock-based compensation (in shares)-Restricted Stock [Member]-->
  <us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements contextRef="c20190101to20190331_AwardTypeAxis_RestrictedStockMember" unitRef="U001" decimals="-3">665000</us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements>
  <!--Shares issuable related to stock-based compensation (in shares)-Employee Stock Option [Member]-->
  <us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements contextRef="c20190101to20190331_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U001" decimals="-3">2252000</us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements>
  <!--Intangible Assets, Finite-Lived, Policy [Policy Text Block]-->
  <us-gaap:IntangibleAssetsFiniteLivedPolicy contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the United States Patent and Trademark Office, or foreign equivalent, issues the patent. We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. We evaluate patents and patent applications that we are not actively pursuing and write off any associated costs.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:IntangibleAssetsFiniteLivedPolicy>
  <!--Interest Expense-->
  <us-gaap:InterestExpense contextRef="c20190101to20190331" unitRef="U002" decimals="-3">11599000</us-gaap:InterestExpense>
  <!--Interest Expense-->
  <us-gaap:InterestExpense contextRef="c20180101to20180331" unitRef="U002" decimals="-3">10938000</us-gaap:InterestExpense>
  <!--Interest Paid, Excluding Capitalized Interest, Operating Activities-->
  <us-gaap:InterestPaidNet contextRef="c20190101to20190331" unitRef="U002" decimals="-3">667000</us-gaap:InterestPaidNet>
  <!--Interest Paid, Excluding Capitalized Interest, Operating Activities-->
  <us-gaap:InterestPaidNet contextRef="c20180101to20180331" unitRef="U002" decimals="-3">644000</us-gaap:InterestPaidNet>
  <!--Inventory Write-down-->
  <us-gaap:InventoryWriteDown contextRef="c20180101to20180331" unitRef="U002" decimals="-3">0</us-gaap:InventoryWriteDown>
  <!--Inventory Write-down-->
  <us-gaap:InventoryWriteDown contextRef="c20190101to20190331" unitRef="U002" decimals="-3">0</us-gaap:InventoryWriteDown>
  <!--Inventory, Net-->
  <us-gaap:InventoryNet contextRef="c20181231" unitRef="U002" decimals="-3">8582000</us-gaap:InventoryNet>
  <!--Inventory, Net-->
  <us-gaap:InventoryNet contextRef="c20190331" unitRef="U002" decimals="-3">11057000</us-gaap:InventoryNet>
  <!--Inventory, Policy [Policy Text Block]-->
  <us-gaap:InventoryPolicyTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Inventory valuation&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or market value under the first-in, first-out method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials they have alternative future uses. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency.&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We obtained the first regulatory approval for TEGSEDI in July 2018. At March 31, 2019 and December 31, 2018, our physical inventory for TEGSEDI included API that we produced prior to when we obtained regulatory approval and accordingly has no cost basis as we had previously expensed the costs as R&amp;amp;D expenses.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We did not record any inventory write-offs for the three months ended March 31, 2019 and 2018. Total inventory was $11.1 million and $8.6 million as of &lt;/font&gt;March 31, 2019 and December 31, 2018&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, respectively.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:InventoryPolicyTextBlock>
  <!--Investment Income, Net-->
  <us-gaap:InvestmentIncomeNet contextRef="c20180101to20180331" unitRef="U002" decimals="-3">3610000</us-gaap:InvestmentIncomeNet>
  <!--Investment Income, Net-->
  <us-gaap:InvestmentIncomeNet contextRef="c20190101to20190331" unitRef="U002" decimals="-3">12142000</us-gaap:InvestmentIncomeNet>
  <!--Investments Classified by Contractual Maturity Date [Table Text Block]-->
  <us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&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 March 31, 2019:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;One year or less&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;74%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;After one year but within two years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;21%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;After two years but within three years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;100%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock>
  <!--Lessee, Operating Lease, Liability, Payments, Due Year Four-->
  <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFour contextRef="c20190331" unitRef="U002" decimals="-3">2539000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFour>
  <!--Lessee, Operating Leases [Text Block]-->
  <us-gaap:LesseeOperatingLeasesTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;5.&amp;#160; Operating Leases&lt;/div&gt;&lt;div&gt;&lt;br /&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 lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing facility. We lease this space under a non-cancelable operating lease with an initial term ending in June 2021 and an option to extend the lease for up to two five-year periods.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We also lease additional office space and we sublease a portion of this space to Akcea. We lease this space under a non-cancelable operating lease with an initial term ending in June 2023 and an option to extend the lease for one five-year period. The sublease with Akcea is eliminated in our condensed consolidated financial statements.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea entered into an operating lease agreement for office space located in Boston, Massachusetts for its new corporate headquarters in the second quarter of 2018. The lease commencement date was in August 2018 and Akcea took occupancy in September 2018. Akcea is leasing this space under a non-cancelable operating lease with an initial term ending after 123 months and an option to extend the lease for an additional five-year term. Under the lease agreement, Akcea received a three-month free rent period, which commenced on August 15, 2018, and a tenant improvement allowance up to $3.8 million. Akcea provided the lessor with a letter of credit to secure its obligations under the lease in the initial amount of $2.4 million, to be reduced to $1.8 million on the third anniversary of the rent commencement date and to $1.2 million on the fifth anniversary of the rent commencement date if Akcea meets certain conditions set forth in the lease at each such time.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases we did not include the extension options for these leases.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts related to our operating leases were as follows (dollar amounts in millions):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;At March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Right-of-use operating lease assets (1)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;13.1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Operating lease liabilities (2)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;18.0&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Weighted average remaining lease term&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;9 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Weighted average discount rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;7.6&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Included in deposits and other assets on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(2)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Current portion of $2.0 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 paid cash of $1.0 million for rent payments we made during the three months ended March 31, 2019, which was included in the measurement of our lease liabilities in our net cash provided by operating activities in our condensed consolidated statement of cash flows.&lt;/div&gt;&lt;div&gt;&lt;br /&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 March 31, 2019, the payments for our operating lease liabilities are as follows (in thousands):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Operating&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Leases&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Remainder of 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,341&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Years ending December 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;3,008&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2021&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,725&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2022&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,539&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2023&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,505&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Thereafter&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;11,862&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total minimum lease payments&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;24,980&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Less:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Imputed interest&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(7,020&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 36.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total operating lease liabilities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;17,960&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#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; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Rent expense was $0.9 million for the three months ended March 31, 2019 and was negligible for the three months ended March 31, 2018.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:LesseeOperatingLeasesTextBlock>
  <!--Lessee, Operating Lease, Liability, Payments, Due Year Two-->
  <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo contextRef="c20190331" unitRef="U002" decimals="-3">3008000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo>
  <!--Lessee, Operating Lease, Term of Contract-Akcea Therapeutics, Inc. [Member]-Office Space for Corporate Headquarters [Member]-->
  <us-gaap:LesseeOperatingLeaseTermOfContract contextRef="c20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember">P123M</us-gaap:LesseeOperatingLeaseTermOfContract>
  <!--Lessee, Operating Lease, Liability, Undiscounted Excess Amount-->
  <us-gaap:LesseeOperatingLeaseLiabilityUndiscountedExcessAmount contextRef="c20190331" unitRef="U002" decimals="-3">7020000</us-gaap:LesseeOperatingLeaseLiabilityUndiscountedExcessAmount>
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  <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue contextRef="c20190331" unitRef="U002" decimals="-3">24980000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue>
  <!--Lessee, Leases [Policy Text Block]-->
  <us-gaap:LesseeLeasesPolicyTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Leases&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Topic 842 Adoption&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In February 2016, the FASB issued amended accounting guidance related to lease accounting. This guidance supersedes the lease requirements we previously followed in Accounting Standards Codification, or ASC, Topic 840, &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Leases&lt;/font&gt;, or Topic 840, and created a new lease accounting standard, Topic 842, &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Leases&lt;/font&gt;, or Topic 842. Under Topic 842, an entity will record on its balance sheet all leases with a term longer than one year. Further, an entity will record a liability with a value equal to the present value of payments it will make over the life of the lease (lease liability) and an asset representing the underlying leased asset (right-of-use asset). The new accounting guidance requires entities to determine if its leases are operating or financing leases. Entities will recognize expense for operating leases on a straight-line basis as an operating expense. If an entity determines a lease is a financing&amp;#160;lease, it will record&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. We adopted Topic 842 on January 1, 2019 and adjusted our opening balance sheet on that date for our right-of-use operating lease assets and operating lease liabilities. At adoption, we recorded $13.5 million in right-of-use operating lease assets and $18.5 million in operating lease liabilities, of which we classified $2 million as a current liability. We adopted Topic 842 using the available practical expedients&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; permitted under the transition guidance within the new standard, which among other things, allowed us to carry forward the historical lease classification of those leases we had in place as of January 1, 2019. &lt;/font&gt;The adoption did not have an impact on our condensed consolidated statement of operations.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Leases&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed consolidated balance sheet for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we will pay over the lease term.&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&amp;#160;&lt;/font&gt;We determined the lease term at the commencement date of the lease, and in certain cases our lease term could include renewal options if we concluded we were reasonably certain that we will exercise the renewal option.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;As our current leases do not provide an interest rate implicit in the lease, we used our or Akcea&amp;#8217;s incremental borrowing rate, based on the information available on the date we adopted Topic 842 in determining the present value of future payments. Our right-of-use operating lease asset also includes any lease payments we made and excludes any tenant improvement allowances we received. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:LesseeLeasesPolicyTextBlock>
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  <!--New Accounting Pronouncements, Policy [Policy Text Block]-->
  <us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Impact of recently issued accounting standards&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. The new standard is effective for annual and interim periods beginning after December 15, 2019. Early adoption is permitted for periods beginning after December 15, 2018. When we adopt the new standard, we will make any adjustments to beginning balances through a cumulative-effect adjustment to accumulated deficit on that date. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it will have on our condensed consolidated financial statements and disclosures.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. The updated guidance is effective for fiscal years beginning after December 31, 2019, and interim periods within those fiscal years. Early adoption is permitted in any interim period. We are currently assessing the effects this updated guidance could have on our condensed consolidated financial statements and timing of adoption.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In August 2018, the FASB updated its disclosure requirements related to Level 1, 2 and 3 fair value measurements. The update included deletion and modification of certain disclosure requirements and additional disclosure related to Level 3 measurements. The guidance is effective for fiscal years beginning after December 31, 2019 and early adoption is permitted. We adopted this updated guidance on January 1, 2019 and it did not have a significant impact on our disclosures.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we will implement it (in italics):&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 72pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;We will apply all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Adds &amp;#8220;unit of account&amp;#8221; concept to collaboration accounting guidance to align with Topic 606. The &amp;#8220;unit of account&amp;#8221; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 72pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;We will use the &amp;#8220;unit of account&amp;#8221; concept when we receive consideration under a collaboration to determine when we recognize revenue or a contra expense&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;3)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 72pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we will not recognize revenue for the transaction&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The updated guidance is effective for public entities for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. 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  <us-gaap:OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1.&amp;#160; Basis of Presentation&lt;/div&gt;&lt;div&gt;&lt;br /&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 months ended March 31, 2019 and 2018 on the same basis as the audited financial statements for the year ended December 31, 2018. 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. Results for the interim periods are not necessarily indicative of the results 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, 2018 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="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In the condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals,&amp;#160;Inc. and the consolidated results of our majority owned affiliate,&amp;#160;Akcea Therapeutics, Inc. and its wholly owned subsidiaries. We formed Akcea in December 2014. &lt;/font&gt;In July 2017, Akcea completed an &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;initial public offering, or IPO,&lt;/font&gt; and therefore, beginning in July 2017, we no longer owned 100 percent of Akcea. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;, increasing our ownership to approximately 76 percent at March 31, 2019. We reflected the increase in our ownership in these financial statements. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Refer to the section titled &amp;#8220;Noncontrolling Interest in Akcea&amp;#8221; in Note 2, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies,&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for further information related to our accounting for our investment in Akcea.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unless the context requires otherwise, &amp;#8220;Ionis&amp;#8221;, &amp;#8220;Company,&amp;#8221; &amp;#8220;we,&amp;#8221; &amp;#8220;our,&amp;#8221; and &amp;#8220;us&amp;#8221; refers to Ionis Pharmaceuticals, Inc. and its majority owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock>
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  <!--Revenue from Contract with Customer [Policy Text Block]-->
  <us-gaap:RevenueFromContractWithCustomerPolicyTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&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;font style="background-color: #FFFFFF;"&gt;Revenue Recognition&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Our Revenue Sources&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts in deferred revenue on our consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Commercial Revenue: TEGSEDI Product Sales, net&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018. &lt;/font&gt;In the U.S., TEGSEDI is distributed through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients. In Germany, TEGSEDI is distributed through a non-exclusive distribution model with a 3PL that takes title to TEGSEDI. The 3PL is our sole customer in Germany. The 3PL in Germany then distributes TEGSEDI to hospitals and pharmacies.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Research and development revenue under collaborative agreements&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We often 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;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We provide details about our collaboration agreements in Note 7, &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements,&lt;/font&gt; in our Annual Report on Form 10-K for the year ended December 31, 2018&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;.&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&amp;#160;&lt;/font&gt;Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Steps to Recognize Revenue&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;1.&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Identify the contract&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We and our partner approved the contract and we are both committed to perform our obligations;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have identified our rights, our partner&amp;#8217;s rights and the payment terms;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We believe collectability is probable.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="margin-bottom: 10pt;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;2.&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Identify the performance obligations&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We next identify the distinct goods and services we are required to provide under the contract. Accounting rules refer to these as our performance obligations. We typically have only one performance obligation at the inception of a contract, which is to perform R&amp;amp;D services.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Often times we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights. These items are contingent upon future events that may not occur. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;3.&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Determine the transaction price&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and are usually based on scientific progress. For example, in the first quarter of 2019, we earned $35 million in milestone payments from Roche when it dosed the first patient in the Phase 3 study of IONIS-HTT&lt;sub&gt;Rx &lt;/sub&gt;(RG6042) &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;because we do not have any performance obligations related to these milestone payments as Roche is conducting the Phase 3 study of IONIS-HTT&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/font&gt; At December 31, 2018, we determined it was not probable that we could earn these milestone payments.&amp;#160;As such, we did not recognize any revenue associated with the milestone payments in 2018.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;4.&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Allocate the transaction price&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Estimated future product sales;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Estimated royalties on future product sales;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Contractual milestone payments;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expenses we expect to incur;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Income taxes; and&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;A discount rate.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We typically estimate the selling price of R&amp;amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;amp;D services include:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The number of internal hours we estimate we will spend performing these services;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The estimated cost of work we will perform;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The estimated cost of work that we will contract with third parties to perform; and&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The estimated cost of API we will use.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For purposes of determining the stand-alone selling price of the R&amp;amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;5.&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Recognize revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For R&amp;amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following are examples of when we typically recognize revenue based on the types of payments we receive.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize royalty revenue in the period in which the counterparty sells the related product, which in certain cases may require us to estimate our royalty revenue. &lt;/font&gt;We recognize royalties from SPINRAZA sales in the period Biogen records the sale of SPINRAZA.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Commercial Revenue: TEGSEDI Product Sales, net&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize TEGSEDI product sales in the period &lt;/font&gt;when our customer obtains control of TEGSEDI, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative expenses in our condensed consolidated statements of operations. Otherwise payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues, taxes collected from customers relating to product sales and remitted to governmental authorities.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Reserves for TEGSEDI Product Sales&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We record TEGSEDI product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates, co-pay assistance and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as reductions of accounts receivable when the amount is payable to our customer or a current liability when the amount is payable to a party other than our customer in our condensed consolidated balance sheet. In certain cases, our estimates include a range of possible outcomes that are probability-weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net TEGSEDI product sales in the respective period.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following are the components of variable consideration related to TEGSEDI product sales:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Chargebacks: &lt;/font&gt;In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We record reserves for these chargebacks related to TEGSEDI product sales to our U.S. customer during the reporting period. We also estimate the amount of product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Government rebates&lt;/font&gt;: We are subject to discount obligations under government programs, including Medicaid programs and Medicare in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability-weighted for the estimated payer mix. We record these reserves as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Trade discounts and allowances: &lt;/font&gt;We provide customary invoice discounts on TEGSEDI product sales to our U.S. customer for prompt payment. We record this discount as a reduction of TEGSEDI product sales in the period in which we recognize the related product revenue. In addition, we receive and pay for various distribution services from our U.S. customer and wholesalers in our U.S. distribution channel. For services we receive that are either not distinct from the sale of TEGSEDI or for which we cannot reasonably estimate the fair value, we classify such fees as a reduction of TEGSEDI product sales.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Product Returns: &lt;/font&gt;Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the TEGSEDI&amp;#8217;s expiration date. We estimate the amount of TEGSEDI product sales that our customer may return. We record our return estimate as an accrued refund liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales, in the same period we recognize the related sale. Based on our distribution model for TEGSEDI, contractual inventory limits with our customer and wholesalers and the price of TEGSEDI, we believe we will have minimal returns. Our customer in Germany only takes title to the product once it receives an order from a hospital or pharmacy and therefore does not maintain any inventory of TEGSEDI, as such we do not estimate returns in Germany.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Other incentives: &lt;/font&gt;In the U.S., we estimate reserves for other incentives including co-payment assistance we provide to patients with commercial insurance who have coverage and reside in states that allow co-payment assistance. We record a reserve for the amount we estimate we will pay for co-payment assistance. We base our reserve on the number of estimated claims and our estimate of the cost per claim related to TEGSEDI product sales that we have recognized as revenue. We record our other incentive reserve estimates as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales, in the same period we recognize the related sale.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Research and development revenue under collaboration agreements:&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Upfront Payments&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;When we enter into a collaboration agreement with an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;amp;D services. For example, under our &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;collaboration agreement with Roche to&lt;/font&gt;&lt;font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; develop IONIS-FB-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;for the treatment of complement-mediated diseases&lt;/font&gt;, we received a $75 million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;amp;D services. We are amortizing the $75 million upfront payment using an input method over the estimated period of time we are providing R&amp;amp;D services.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Milestone Payments&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because there is considerable uncertainty in the research and development processes that trigger these payments under our collaboration agreements. 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 we achieve the milestone under the sales-based royalty exception allowed under accounting rules.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the third quarter of 2017, we initiated a Phase 1/2a clinical study of IONIS-MAPT&lt;sub&gt;Rx &lt;/sub&gt;in patients with mild Alzheimer&amp;#8217;s disease. We earned a $10 million milestone payment from Biogen related to the initiation of this study. We added this payment to the transaction price and allocated it to our R&amp;amp;D services performance obligation. We are recognizing revenue from this milestone payment over our estimated period of performance.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Conversely, we recognize in full those milestone payments that we earn based on our partners&amp;#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the first quarter of 2019, we recognized $35 million in milestone payments &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;when Roche dosed the first patient in a Phase 3 study for IONIS-HTT&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We concluded that the milestone payments were not related to our R&amp;amp;D services performance obligation. Therefore, we recognized these milestone payments in full in the first quarter of 2019.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;License Fees&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We generally recognize as revenue the total amount we determine to be the stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. &lt;/font&gt;For example, in the first quarter of 2019, we earned a $150 million license fee when Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; from us.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Amendments to Agreements&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;If the goods and/or services are at a stand-alone selling price.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and at their stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the prevention of thrombosis. As part of the agreement, Bayer paid us a $100 million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and to initiate development of IONIS-FXI-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $75 million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and IONIS-FXI-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Under the 2017 amendment, we concluded we had a new agreement with three performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, to provide R&amp;amp;D services and to deliver API. We allocated the $75 million transaction price to these performance obligations. &lt;/font&gt;Refer to &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note 7, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/font&gt;, for further discussion &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;of our accounting treatment for our Bayer collaboration.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Multiple Agreements&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Whether the goods and/or services promised under the agreements are a single performance obligation.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:RevenueFromContractWithCustomerPolicyTextBlock>
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  <us-gaap:RevenueRecognitionPolicyTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Deferred Revenue&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are often entitled to bill our customers and receive payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue on our condensed consolidated balance sheet.&lt;/font&gt; During the three months ended March 31, 2019 and 2018, we recognized $40.3 million and $34.9 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:RevenueRecognitionPolicyTextBlock>
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  <us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis ESPP:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1.6%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;45.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;44.4%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock>
  <!--Schedule of Share-based Payment Award, Employee Stock Purchase Plan, Valuation Assumptions [Table Text Block]-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock contextRef="c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Akcea ESPP:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1.6%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;64.1%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;62.3%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock>
  <!--Schedule of Share-based Payment Award, Stock Options, Valuation Assumptions [Table Text Block]-->
  <us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the three months ended March 31, 2019 and 2018, 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="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Ionis Employee Stock Options:&lt;/font&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.4%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.2%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;60.3%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;63.2%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;4.6 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;4.6 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock>
  <!--Schedule of Share-based Payment Award, Stock Options, Valuation Assumptions [Table Text Block]-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock contextRef="c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div&gt;&lt;br /&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 addition to our stock plans, Akcea has its own stock plan under which it grants options and RSUs and under which it derives its stock-based compensation expense. The following are the weighted-average Black-Scholes assumptions Akcea used under its plan for the three months ended March 31, 2019 and March 31, 2018:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Akcea Employee Stock Options:&lt;/font&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.6%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;76.4%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;77.1%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6.1 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6.1 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock>
  <!--Schedule of Earnings Per Share, Basic and Diluted [Table Text Block]-->
  <us-gaap:ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our diluted net income per share for the three months ended March 31, 2019 as follows (in thousands except per share amounts):&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three months ended March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Income&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Numerator)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Shares&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Denominator)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Per-Share&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Amount&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Net income available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;87,543&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;138,582&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.63&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Effect of dilutive securities:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Shares issuable upon exercise of stock options&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,252&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Shares issuable upon restricted stock award issuance&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;665&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Shares issuable related to our ESPP&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;38&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Income available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;87,543&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;141,537&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.62&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock>
  <!--Schedule of Temporary Impairment Losses, Investments [Table Text Block]-->
  <us-gaap:ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&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 March 31, 2019. 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. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&amp;#8217; amortized cost basis at maturity.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table border="0" cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 30%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Less than 12 Months of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Temporary Impairment&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;More than 12 Months of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Temporary Impairment&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Total Temporary&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Impairment&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 30%;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;(In thousands)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Number of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Investments&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Estimated&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Fair Value&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Unrealized&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Losses&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Estimated&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Fair Value&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Unrealized&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Losses&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Estimated&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Fair Value&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Unrealized&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Losses&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 30%; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Corporate debt securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;275&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;530,786&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(306&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;102,815&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(561&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 30%; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by U.S. government agencies&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; 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width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(81&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;107,539&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(255, 255, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(127&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 30%; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by the U.S. Treasury&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;15&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;94,603&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(34&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 30%; padding-bottom: 2px; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;39&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;11,254&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;51,579&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(319&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;62,833&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(328&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 30%; padding-bottom: 4px; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total temporarily impaired securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;353&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;727,648&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(430&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;170,928&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(926&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;898,576&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1,356&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock>
  <!--Schedule of Future Minimum Lease Payments for Capital Leases [Table Text Block]-->
  <us-gaap:ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of March 31, 2019, the payments for our operating lease liabilities are as follows (in thousands):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Operating&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Leases&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Remainder of 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,341&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Years ending December 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;3,008&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2021&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,725&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2022&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,539&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2023&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,505&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Thereafter&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;11,862&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total minimum lease payments&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;24,980&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Less:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 18.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Imputed interest&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(7,020&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 36.7pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total operating lease liabilities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;17,960&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock>
  <!--Schedule of Earnings Per Share, Basic, by Common Class, Including Two Class Method [Table Text Block]-->
  <us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net income per share for the three months ended &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;March 31, 2019&lt;/font&gt;, was calculated as follows (in thousands, except per share amounts):&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three months ended March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Weighted&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Average Shares&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Owned in Akcea&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Net Income&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Per Share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Ionis&amp;#8217; Portion of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s Net Loss&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Common shares&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;68,582&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.35&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;23,846&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea&amp;#8217;s net income attributable to our ownership&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;23,846&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;63,697&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Net income available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;87,543&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Weighted average shares outstanding&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;138,582&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Basic net income per share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.63&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#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; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net loss per share for the three months ended &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;March 31, 2018&lt;/font&gt;, was calculated as follows (in thousands, except per share amounts):&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three months ended March 31, 2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Weighted&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Average Shares&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Owned in Akcea&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Net Loss&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Per Share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Ionis&amp;#8217; Portion of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s Net Loss&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Common shares&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;45,448&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(0.44&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(19,997&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(19,997&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;18,785&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Net loss available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1,212&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Weighted average shares outstanding&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;125,330&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Basic net loss per share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(0.01&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock>
  <!--Schedule of Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Table Text Block]-->
  <us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&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 months ended March 31, 2019 and 2018 (in thousands). Our non-cash stock-based compensation expense includes $18.6 million and $6.4 million of stock-based compensation expense for Akcea employees for the three months ended March 31, 2019 and 2018, respectively.&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;/font&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt; 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Cost of products sold&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;118&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Research, development and patent&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;24,435&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;19,682&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Selling, general and administrative&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;20,952&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;8,769&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;45,505&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;28,451&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock>
  <!--Schedule of Segment Reporting Information, by Segment [Table Text Block]-->
  <us-gaap:ScheduleOfSegmentReportingInformationBySegmentTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following tables show our segment revenue and income (loss) from operations for the three months ended March 31, 2019 and March 31, 2018 (in thousands), respectively.&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Ionis Core&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea Therapeutics&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Elimination of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Intercompany Activity&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Revenue:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="text-align: left; margin-left: 7.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Commercial revenue:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;SPINRAZA royalties&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;59,711&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;59,711&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;TEGSEDI product sales, net&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6,754&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6,754&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Licensing and other royalty revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,623&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,623&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 43.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total commercial revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;61,334&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6,754&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;68,088&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 7.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;160,556&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;157,062&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(88,492&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;229,126&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total segment revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;221,890&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;163,816&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(88,492&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;297,214&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total operating expenses&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;114,515&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; 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text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(12,046&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="text-align: left; margin-left: 7.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Commercial revenue:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;SPINRAZA royalties&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Licensing and other royalty revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;942&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; 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padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;942&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 43.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total commercial revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;42,023&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;42,023&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 7.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;90,517&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;17,108&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(5,229&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;102,396&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total segment revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;132,540&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;17,108&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(5,229&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;144,419&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total operating expense&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;105,544&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;47,435&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(5,259&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;147,720&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Income (loss) from operations&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;26,996&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(30,327&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;30&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(3,301&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following table shows our total assets by segment at March 31, 2019 and December 31, 2018 (in thousands), respectively.&lt;/font&gt;&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Total Assets&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Ionis Core&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea Therapeutics&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Elimination of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Intercompany Activity&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;3,112,235&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;458,717&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(735,063&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,835,889&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;December 31, 2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,975,491&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;365,261&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(672,968&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,667,784&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ScheduleOfSegmentReportingInformationBySegmentTextBlock>
  <!--Schedules of Concentration of Risk, by Risk Factor [Table Text Block]-Collaborative Arrangements and Licensing Agreements, Roche [Member]-->
  <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock contextRef="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt; 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;R&amp;amp;D revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;41.2&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.0&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Percentage of total revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;14&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock>
  <!--Schedules of Concentration of Risk, by Risk Factor [Table Text Block]-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock contextRef="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt; 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;R&amp;amp;D revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;157.1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;17.1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Percentage of total revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;53&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;12&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock>
  <!--Schedules of Concentration of Risk, by Risk Factor [Table Text Block]-Collaborative Arrangements and Licensing Agreements, Biogen [Member]-->
  <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock contextRef="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt; 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;SPINRAZA royalties (commercial revenue)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;59.7&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;41.1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;R&amp;amp;D revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;24.5&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;10.8&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total revenue from our relationship with Biogen&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;84.2&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;51.9&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Percentage of total revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;28&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;36&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock>
  <!--Segment Reporting, Policy [Policy Text Block]-->
  <us-gaap:SegmentReportingPolicyPolicyTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Segment information&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have two operating segments, our Ionis Core segment and Akcea Therapeutics, our majority-owned affiliate. Akcea is &lt;/font&gt;a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We provide segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviews to assess operating performance and to make operating decisions. We allocate a portion of Ionis&amp;#8217; development, R&amp;amp;D support and general and administrative expenses to Akcea for work Ionis performs on behalf of Akcea.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:SegmentReportingPolicyPolicyTextBlock>
  <!--Segment Reporting Disclosure [Text Block]-->
  <us-gaap:SegmentReportingDisclosureTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;8.&amp;#160; Segment Information&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have two reportable segments Ionis Core and Akcea Therapeutics. &lt;/font&gt;At &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;March 31, 2019 &lt;/font&gt;we owned approximately 76 percent of Akcea.&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In our Ionis Core segment we are exploiting our antisense technology to generate a broad pipeline of first-in-class and/or best-in-class medicines for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea is &lt;/font&gt;a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Akcea generates revenue from TEGSEDI product sales and from its collaborations with Novartis and PTC Therapeutics.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 show our segment revenue and income (loss) from operations for the three months ended March 31, 2019 and March 31, 2018 (in thousands), respectively.&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Ionis Core&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea Therapeutics&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Elimination of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Intercompany Activity&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Revenue:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="text-align: left; margin-left: 7.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Commercial revenue:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;SPINRAZA royalties&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;59,711&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;59,711&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;TEGSEDI product sales, net&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6,754&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6,754&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Licensing and other royalty revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,623&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,623&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 43.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total commercial revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;61,334&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6,754&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;68,088&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 7.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;160,556&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;157,062&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(88,492&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;26,206&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Elimination of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Intercompany Activity&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Revenue:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="text-align: left; margin-left: 7.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Commercial revenue:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;SPINRAZA royalties&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;41,081&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;41,081&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Licensing and other royalty revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;942&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;942&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 43.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total commercial revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;42,023&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;42,023&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 7.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;90,517&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;17,108&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(5,229&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;102,396&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 25.2pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total segment revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;132,540&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;17,108&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(5,229&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;144,419&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; 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font-family: 'Times New Roman', Times, serif;"&gt;47,435&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(5,259&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;147,720&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; 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border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;26,996&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(30,327&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;30&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(3,301&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following table shows our total assets by segment at March 31, 2019 and December 31, 2018 (in thousands), respectively.&lt;/font&gt;&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Total Assets&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Ionis Core&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea Therapeutics&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Elimination of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Intercompany Activity&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;3,112,235&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;458,717&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(735,063&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,835,889&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;December 31, 2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,975,491&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;365,261&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(672,968&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,667,784&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:SegmentReportingDisclosureTextBlock>
  <!--Selling, General and Administrative Expense-->
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  <!--Selling, General and Administrative Expense-->
  <us-gaap:SellingGeneralAndAdministrativeExpense contextRef="c20190101to20190331" unitRef="U002" decimals="-3">68221000</us-gaap:SellingGeneralAndAdministrativeExpense>
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  <!--Share-based Compensation-->
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  <!--Share-based Compensation-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate-Employee Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate-Employee Stock [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate-Employee Stock Option [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate-Employee Stock [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate-Employee Stock Option [Member]-Akcea Therapeutics, Inc. [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate-Akcea Therapeutics, Inc. [Member]-Employee Stock Option [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate-Employee Stock Option [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate-Akcea Therapeutics, Inc. [Member]-Employee Stock [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Weighted Average Volatility Rate-Employee Stock [Member]-->
  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate contextRef="c20180101to20180331_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3">0.444</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Weighted Average Volatility Rate-Akcea Therapeutics, Inc. [Member]-Employee Stock [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Weighted Average Volatility Rate-Employee Stock Option [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Weighted Average Volatility Rate-Employee Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Weighted Average Volatility Rate-Employee Stock Option [Member]-Akcea Therapeutics, Inc. [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Weighted Average Volatility Rate-Employee Stock [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Weighted Average Volatility Rate-Akcea Therapeutics, Inc. [Member]-Employee Stock Option [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Weighted Average Volatility Rate-Employee Stock Option [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Risk Free Interest Rate-Employee Stock Option [Member]-Akcea Therapeutics, Inc. [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Risk Free Interest Rate-Akcea Therapeutics, Inc. [Member]-Employee Stock Option [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Risk Free Interest Rate-Akcea Therapeutics, Inc. [Member]-Employee Stock [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Risk Free Interest Rate-Employee Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
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  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Risk Free Interest Rate-Employee Stock [Member]-->
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  <!--Share-based Compensation, Option and Incentive Plans Policy [Policy Text Block]-->
  <us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock-based compensation expense&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We measure stock-based compensation expense for equity-classified awards, principally related to stock options, restricted stock units, or RSUs, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the three months ended March 31, 2019 and 2018, 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="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Ionis Employee Stock Options:&lt;/font&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.4%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.2%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;60.3%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;63.2%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;4.6 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;4.6 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis ESPP:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1.6%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;45.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;44.4%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. RSUs vest annually over a four-year period. The weighted-average grant date fair value of RSUs granted to employees for the three months ended March 31, 2019 was $58.26 per share.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 addition to our stock plans, Akcea has its own stock plan under which it grants options and RSUs and under which it derives its stock-based compensation expense. The following are the weighted-average Black-Scholes assumptions Akcea used under its plan for the three months ended March 31, 2019 and March 31, 2018:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Akcea Employee Stock Options:&lt;/font&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.6%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;76.4%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;77.1%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6.1 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6.1 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Akcea ESPP:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1.6%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;64.1%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;62.3%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="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 months ended March 31, 2019 and 2018 (in thousands). Our non-cash stock-based compensation expense includes $18.6 million and $6.4 million of stock-based compensation expense for Akcea employees for the three months ended March 31, 2019 and 2018, respectively.&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;/font&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt; 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Cost of products sold&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;118&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Research, development and patent&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;24,435&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;19,682&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Selling, general and administrative&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;20,952&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;8,769&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;45,505&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;28,451&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#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; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of March 31, 2019, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $192.2 million and $68.7 million, respectively. We will adjust total unrecognized compensation cost for future forfeitures. We expect to recognize the cost of non-cash stock-based compensation expense related to non-vested stock options and RSUs over a weighted average amortization period of 1.4 years and 2.0 years, respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy>
  <!--Shares Paid for Tax Withholding for Share Based Compensation-Common Stock [Member]-->
  <us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation contextRef="c20190101to20190331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3">130000</us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation>
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  <us-gaap:SharesIssued contextRef="c20181231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3">137929000</us-gaap:SharesIssued>
  <!--Shares, Issued-Common Stock [Member]-->
  <us-gaap:SharesIssued contextRef="c20171231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3">124976000</us-gaap:SharesIssued>
  <!--Shares, Issued-Common Stock [Member]-->
  <us-gaap:SharesIssued contextRef="c20180331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3">125449000</us-gaap:SharesIssued>
  <!--Shares, Issued-Common Stock [Member]-->
  <us-gaap:SharesIssued contextRef="c20190331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3">139624000</us-gaap:SharesIssued>
  <!--Significant Accounting Policies [Text Block]-->
  <us-gaap:SignificantAccountingPoliciesTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2.&amp;#160; Significant Accounting Policies&lt;/div&gt;&lt;div&gt;&lt;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;font style="background-color: #FFFFFF;"&gt;Revenue Recognition&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Our Revenue Sources&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts in deferred revenue on our consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Commercial Revenue: TEGSEDI Product Sales, net&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018. &lt;/font&gt;In the U.S., TEGSEDI is distributed through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients. In Germany, TEGSEDI is distributed through a non-exclusive distribution model with a 3PL that takes title to TEGSEDI. The 3PL is our sole customer in Germany. The 3PL in Germany then distributes TEGSEDI to hospitals and pharmacies.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Research and development revenue under collaborative agreements&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We often 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;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We provide details about our collaboration agreements in Note 7, &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements,&lt;/font&gt; in our Annual Report on Form 10-K for the year ended December 31, 2018&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;.&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&amp;#160;&lt;/font&gt;Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Steps to Recognize Revenue&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;1.&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Identify the contract&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We and our partner approved the contract and we are both committed to perform our obligations;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have identified our rights, our partner&amp;#8217;s rights and the payment terms;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We believe collectability is probable.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="margin-bottom: 10pt;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;2.&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Identify the performance obligations&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We next identify the distinct goods and services we are required to provide under the contract. Accounting rules refer to these as our performance obligations. We typically have only one performance obligation at the inception of a contract, which is to perform R&amp;amp;D services.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Often times we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights. These items are contingent upon future events that may not occur. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;3.&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Determine the transaction price&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and are usually based on scientific progress. For example, in the first quarter of 2019, we earned $35 million in milestone payments from Roche when it dosed the first patient in the Phase 3 study of IONIS-HTT&lt;sub&gt;Rx &lt;/sub&gt;(RG6042) &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;because we do not have any performance obligations related to these milestone payments as Roche is conducting the Phase 3 study of IONIS-HTT&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/font&gt; At December 31, 2018, we determined it was not probable that we could earn these milestone payments.&amp;#160;As such, we did not recognize any revenue associated with the milestone payments in 2018.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;4.&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Allocate the transaction price&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Estimated future product sales;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Estimated royalties on future product sales;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Contractual milestone payments;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expenses we expect to incur;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Income taxes; and&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;A discount rate.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We typically estimate the selling price of R&amp;amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;amp;D services include:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The number of internal hours we estimate we will spend performing these services;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The estimated cost of work we will perform;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The estimated cost of work that we will contract with third parties to perform; and&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The estimated cost of API we will use.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For purposes of determining the stand-alone selling price of the R&amp;amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;5.&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Recognize revenue&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For R&amp;amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following are examples of when we typically recognize revenue based on the types of payments we receive.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize royalty revenue in the period in which the counterparty sells the related product, which in certain cases may require us to estimate our royalty revenue. &lt;/font&gt;We recognize royalties from SPINRAZA sales in the period Biogen records the sale of SPINRAZA.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Commercial Revenue: TEGSEDI Product Sales, net&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize TEGSEDI product sales in the period &lt;/font&gt;when our customer obtains control of TEGSEDI, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative expenses in our condensed consolidated statements of operations. Otherwise payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues, taxes collected from customers relating to product sales and remitted to governmental authorities.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Reserves for TEGSEDI Product Sales&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We record TEGSEDI product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates, co-pay assistance and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as reductions of accounts receivable when the amount is payable to our customer or a current liability when the amount is payable to a party other than our customer in our condensed consolidated balance sheet. In certain cases, our estimates include a range of possible outcomes that are probability-weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net TEGSEDI product sales in the respective period.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following are the components of variable consideration related to TEGSEDI product sales:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Chargebacks: &lt;/font&gt;In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We record reserves for these chargebacks related to TEGSEDI product sales to our U.S. customer during the reporting period. We also estimate the amount of product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Government rebates&lt;/font&gt;: We are subject to discount obligations under government programs, including Medicaid programs and Medicare in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability-weighted for the estimated payer mix. We record these reserves as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Trade discounts and allowances: &lt;/font&gt;We provide customary invoice discounts on TEGSEDI product sales to our U.S. customer for prompt payment. We record this discount as a reduction of TEGSEDI product sales in the period in which we recognize the related product revenue. In addition, we receive and pay for various distribution services from our U.S. customer and wholesalers in our U.S. distribution channel. For services we receive that are either not distinct from the sale of TEGSEDI or for which we cannot reasonably estimate the fair value, we classify such fees as a reduction of TEGSEDI product sales.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Product Returns: &lt;/font&gt;Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the TEGSEDI&amp;#8217;s expiration date. We estimate the amount of TEGSEDI product sales that our customer may return. We record our return estimate as an accrued refund liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales, in the same period we recognize the related sale. Based on our distribution model for TEGSEDI, contractual inventory limits with our customer and wholesalers and the price of TEGSEDI, we believe we will have minimal returns. Our customer in Germany only takes title to the product once it receives an order from a hospital or pharmacy and therefore does not maintain any inventory of TEGSEDI, as such we do not estimate returns in Germany.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Other incentives: &lt;/font&gt;In the U.S., we estimate reserves for other incentives including co-payment assistance we provide to patients with commercial insurance who have coverage and reside in states that allow co-payment assistance. We record a reserve for the amount we estimate we will pay for co-payment assistance. We base our reserve on the number of estimated claims and our estimate of the cost per claim related to TEGSEDI product sales that we have recognized as revenue. We record our other incentive reserve estimates as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales, in the same period we recognize the related sale.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Research and development revenue under collaboration agreements:&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Upfront Payments&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;When we enter into a collaboration agreement with an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;amp;D services. For example, under our &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;collaboration agreement with Roche to&lt;/font&gt;&lt;font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; develop IONIS-FB-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;for the treatment of complement-mediated diseases&lt;/font&gt;, we received a $75 million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;amp;D services. We are amortizing the $75 million upfront payment using an input method over the estimated period of time we are providing R&amp;amp;D services.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;Milestone Payments&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because there is considerable uncertainty in the research and development processes that trigger these payments under our collaboration agreements. 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 we achieve the milestone under the sales-based royalty exception allowed under accounting rules.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the third quarter of 2017, we initiated a Phase 1/2a clinical study of IONIS-MAPT&lt;sub&gt;Rx &lt;/sub&gt;in patients with mild Alzheimer&amp;#8217;s disease. We earned a $10 million milestone payment from Biogen related to the initiation of this study. We added this payment to the transaction price and allocated it to our R&amp;amp;D services performance obligation. We are recognizing revenue from this milestone payment over our estimated period of performance.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Conversely, we recognize in full those milestone payments that we earn based on our partners&amp;#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the first quarter of 2019, we recognized $35 million in milestone payments &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;when Roche dosed the first patient in a Phase 3 study for IONIS-HTT&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We concluded that the milestone payments were not related to our R&amp;amp;D services performance obligation. Therefore, we recognized these milestone payments in full in the first quarter of 2019.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;License Fees&lt;/u&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We generally recognize as revenue the total amount we determine to be the stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. &lt;/font&gt;For example, in the first quarter of 2019, we earned a $150 million license fee when Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; from us.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Amendments to Agreements&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;If the goods and/or services are at a stand-alone selling price.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and at their stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the prevention of thrombosis. As part of the agreement, Bayer paid us a $100 million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and to initiate development of IONIS-FXI-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $75 million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and IONIS-FXI-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Under the 2017 amendment, we concluded we had a new agreement with three performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L&lt;/font&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, to provide R&amp;amp;D services and to deliver API. We allocated the $75 million transaction price to these performance obligations. &lt;/font&gt;Refer to &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note 7, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/font&gt;, for further discussion &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;of our accounting treatment for our Bayer collaboration.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;Multiple Agreements&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Whether the goods and/or services promised under the agreements are a single performance obligation.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contracts Receivable&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our contracts receivable balance represents the amounts we have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contract receivable to be unconditional. We typically receive payment within one quarter of billing our partner or customer&lt;/font&gt;.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unbilled SPINRAZA Royalties&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen for SPINRAZA royalties. We include these unbilled amounts in other current assets on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Products Sold&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our cost of products sold includes manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of TEGSEDI. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of products sold. Prior to obtaining regulatory approval in July 2018, we expensed a significant portion of the costs we incurred to produce the TEGSEDI supply we are using in the commercial launch as research and development expense. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We previously recognized $0.3 million of costs to produce TEGSEDI related to the TEGSEDI commercial revenue we recognized in the&lt;/font&gt; three months ended March 31, 2019.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;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;Noncontrolling Interest in Akcea Therapeutics, Inc.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Prior to Akcea&amp;#8217;s IPO in July 2017, we owned 100 percent of Akcea. From the closing of Akcea&amp;#8217;s IPO in July 2017 through mid-April 2018, we owned approximately 68 percent&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;of Akcea. In the second, third and fourth quarters of 2018, we received additional shares of Akcea&amp;#8217;s stock related to our license of TEGSEDI and AKCEA-TTR-L&lt;sub&gt;Rx&lt;/sub&gt; to Akcea, increasing our ownership percentage to approximately 75 percent. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;, increasing our ownership to approximately 76 percent at March 31, 2019. We reflected this increase in our ownership percentage in these financial statements as an adjustment to noncontrolling interest. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The shares third parties own represent an interest in Akcea&amp;#8217;s equity that is not controlled by us. However, as we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our condensed consolidated financial statements. We reflect the noncontrolling interest attributable to other owners of Akcea&amp;#8217;s common stock in a separate line on the statement of operations and a separate line within stockholders&amp;#8217; equity in our condensed consolidated balance sheet. In addition, we record a noncontrolling interest adjustment to account for the stock options Akcea grants, which if exercised, will dilute our ownership in Akcea. This adjustment is a reclassification within stockholders&amp;#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cash, cash equivalents and investments&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &amp;#8220;available-for-sale&amp;#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments. We use the specific identification method to determine the cost of securities sold.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At March 31, 2019, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in four privately-held companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Inventory valuation&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or market value under the first-in, first-out method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials they have alternative future uses. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency.&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We obtained the first regulatory approval for TEGSEDI in July 2018. At March 31, 2019 and December 31, 2018, our physical inventory for TEGSEDI included API that we produced prior to when we obtained regulatory approval and accordingly has no cost basis as we had previously expensed the costs as R&amp;amp;D expenses.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We did not record any inventory write-offs for the three months ended March 31, 2019 and 2018. Total inventory was $11.1 million and $8.6 million as of &lt;/font&gt;March 31, 2019 and December 31, 2018&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, respectively.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Leases&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Topic 842 Adoption&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In February 2016, the FASB issued amended accounting guidance related to lease accounting. This guidance supersedes the lease requirements we previously followed in Accounting Standards Codification, or ASC, Topic 840, &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Leases&lt;/font&gt;, or Topic 840, and created a new lease accounting standard, Topic 842, &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Leases&lt;/font&gt;, or Topic 842. Under Topic 842, an entity will record on its balance sheet all leases with a term longer than one year. Further, an entity will record a liability with a value equal to the present value of payments it will make over the life of the lease (lease liability) and an asset representing the underlying leased asset (right-of-use asset). The new accounting guidance requires entities to determine if its leases are operating or financing leases. Entities will recognize expense for operating leases on a straight-line basis as an operating expense. If an entity determines a lease is a financing&amp;#160;lease, it will record&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. We adopted Topic 842 on January 1, 2019 and adjusted our opening balance sheet on that date for our right-of-use operating lease assets and operating lease liabilities. At adoption, we recorded $13.5 million in right-of-use operating lease assets and $18.5 million in operating lease liabilities, of which we classified $2 million as a current liability. We adopted Topic 842 using the available practical expedients&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; permitted under the transition guidance within the new standard, which among other things, allowed us to carry forward the historical lease classification of those leases we had in place as of January 1, 2019. &lt;/font&gt;The adoption did not have an impact on our condensed consolidated statement of operations.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Leases&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed consolidated balance sheet for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we will pay over the lease term.&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&amp;#160;&lt;/font&gt;We determined the lease term at the commencement date of the lease, and in certain cases our lease term could include renewal options if we concluded we were reasonably certain that we will exercise the renewal option.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;As our current leases do not provide an interest rate implicit in the lease, we used our or Akcea&amp;#8217;s incremental borrowing rate, based on the information available on the date we adopted Topic 842 in determining the present value of future payments. Our right-of-use operating lease asset also includes any lease payments we made and excludes any tenant improvement allowances we received. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Research, development and patent expenses&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our condensed consolidated balance sheet and we expense them as the services are provided.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the United States Patent and Trademark Office, or foreign equivalent, issues the patent. We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. We evaluate patents and patent applications that we are not actively pursuing and write off any associated costs.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income Taxes&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act of 2017, or the Tax Act. The Tax Act created a new requirement on global intangible low-taxed income, or GILTI, earned by foreign subsidiaries for tax years beginning on or after January 1, 2018. The GILTI provisions require foreign subsidiary earnings in excess of an allowable return on the foreign subsidiary&amp;#8217;s assets to be included in our U.S. income tax return. Under U.S. GAAP, we are permitted to make an accounting policy election to either treat taxes due on future inclusions in U.S. taxable income related to GILTI as a current-period expense when incurred or to factor such amounts into our measurement of deferred taxes. We have made the election to account for GILTI as a component of current taxes incurred rather than as a component of deferred taxes.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Long-lived assets&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We evaluate long-lived assets, which include property, plant and equipment, right-of-use operating lease assets and patent costs acquired from third parties, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;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="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The preparation of condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States requires 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 those estimates.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;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 and diluted net income (loss) per share&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Basic net income (loss) per share&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The calculation of total net income (loss) attributable to our common stockholders for the three months ended March 31, 2019 and 2018 considered our net income for Ionis on a stand-alone basis plus our share of Akcea&amp;#8217;s net loss for the period. To calculate the portion of Akcea&amp;#8217;s net loss attributable to our ownership, we multiplied Akcea&amp;#8217;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our&amp;#160;total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 basic net income per share for the three months ended &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;March 31, 2019&lt;/font&gt;, was calculated as follows (in thousands, except per share amounts):&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three months ended March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Weighted&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Average Shares&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Owned in Akcea&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Net Income&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Per Share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Ionis&amp;#8217; Portion of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s Net Loss&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Common shares&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;68,582&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.35&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;23,846&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea&amp;#8217;s net income attributable to our ownership&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;23,846&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;63,697&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Net income available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;87,543&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Weighted average shares outstanding&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;138,582&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Basic net income per share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.63&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#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; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net loss per share for the three months ended &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;March 31, 2018&lt;/font&gt;, was calculated as follows (in thousands, except per share amounts):&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three months ended March 31, 2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Weighted&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Average Shares&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Owned in Akcea&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Net Loss&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Per Share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Ionis&amp;#8217; Portion of&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&amp;#8217;s Net Loss&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Common shares&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;45,448&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(0.44&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(19,997&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(19,997&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;18,785&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Net loss available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1,212&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Weighted average shares outstanding&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;125,330&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Basic net loss per share&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(0.01&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Dilutive net income (loss per share)&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For the three months ended March 31, 2019, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 diluted net income per share for the three months ended March 31, 2019 as follows (in thousands except per share amounts):&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three months ended March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Income&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Numerator)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Shares&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;(Denominator)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Per-Share&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Amount&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Net income available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;87,543&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;138,582&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.63&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Effect of dilutive securities:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Shares issuable upon exercise of stock options&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,252&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Shares issuable upon restricted stock award issuance&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;665&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Shares issuable related to our ESPP&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;38&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Income available to Ionis common stockholders&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;87,543&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;141,537&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.62&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#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; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three months ended March 31, 2019, the calculation excluded the 1 percent notes because the effect on diluted earnings per share was anti-dilutive.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For the three months ended March 31, 2018, 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;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1 percent convertible senior notes;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dilutive stock options;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Unvested restricted stock units; and&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Employee Stock Purchase Plan, or ESPP.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Convertible debt&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We account for convertible debt instruments that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate. We determine the carrying amount of the liability component by measuring the fair value of similar debt instruments that do not have the conversion feature. If no similar debt instrument exists, we estimate fair value by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities. To determine the fair value of the debt component we are required to use accounting estimates and assumptions. These estimates and assumptions are judgmental in nature and could have a significant impact on the determination of the debt component, and the associated non-cash interest expense.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;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;Segment information&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have two operating segments, our Ionis Core segment and Akcea Therapeutics, our majority-owned affiliate. Akcea is &lt;/font&gt;a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We provide segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviews to assess operating performance and to make operating decisions. We allocate a portion of Ionis&amp;#8217; development, R&amp;amp;D support and general and administrative expenses to Akcea for work Ionis performs on behalf of Akcea.&lt;/font&gt;&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;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;Stock-based compensation expense&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We measure stock-based compensation expense for equity-classified awards, principally related to stock options, restricted stock units, or RSUs, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the three months ended March 31, 2019 and 2018, 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="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Ionis Employee Stock Options:&lt;/font&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.4%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.2%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;60.3%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;63.2%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;4.6 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;4.6 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis ESPP:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1.6%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.0%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;45.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;44.4%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. RSUs vest annually over a four-year period. The weighted-average grant date fair value of RSUs granted to employees for the three months ended March 31, 2019 was $58.26 per share.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&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 addition to our stock plans, Akcea has its own stock plan under which it grants options and RSUs and under which it derives its stock-based compensation expense. The following are the weighted-average Black-Scholes assumptions Akcea used under its plan for the three months ended March 31, 2019 and March 31, 2018:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Akcea Employee Stock Options:&lt;/font&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.6%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;76.4%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;77.1%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6.1 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6.1 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Akcea ESPP:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Risk-free interest rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.5%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1.6%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Dividend yield&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Volatility&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;64.1%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;62.3%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Expected life&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;6 months&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="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 months ended March 31, 2019 and 2018 (in thousands). Our non-cash stock-based compensation expense includes $18.6 million and $6.4 million of stock-based compensation expense for Akcea employees for the three months ended March 31, 2019 and 2018, respectively.&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;/font&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Three Months Ended&lt;/font&gt;&lt;/div&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;March 31,&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt; 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Cost of products sold&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;118&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Research, development and patent&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;24,435&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;19,682&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Selling, general and administrative&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;20,952&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;8,769&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;45,505&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;28,451&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#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; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of March 31, 2019, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $192.2 million and $68.7 million, respectively. We will adjust total unrecognized compensation cost for future forfeitures. We expect to recognize the cost of non-cash stock-based compensation expense related to non-vested stock options and RSUs over a weighted average amortization period of 1.4 years and 2.0 years, respectively.&lt;/div&gt;&lt;div&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;Impact of recently issued accounting standards&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. The new standard is effective for annual and interim periods beginning after December 15, 2019. Early adoption is permitted for periods beginning after December 15, 2018. When we adopt the new standard, we will make any adjustments to beginning balances through a cumulative-effect adjustment to accumulated deficit on that date. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it will have on our condensed consolidated financial statements and disclosures.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. The updated guidance is effective for fiscal years beginning after December 31, 2019, and interim periods within those fiscal years. Early adoption is permitted in any interim period. We are currently assessing the effects this updated guidance could have on our condensed consolidated financial statements and timing of adoption.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In August 2018, the FASB updated its disclosure requirements related to Level 1, 2 and 3 fair value measurements. The update included deletion and modification of certain disclosure requirements and additional disclosure related to Level 3 measurements. The guidance is effective for fiscal years beginning after December 31, 2019 and early adoption is permitted. We adopted this updated guidance on January 1, 2019 and it did not have a significant impact on our disclosures.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we will implement it (in italics):&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 72pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;We will apply all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Adds &amp;#8220;unit of account&amp;#8221; concept to collaboration accounting guidance to align with Topic 606. The &amp;#8220;unit of account&amp;#8221; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 72pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;We will use the &amp;#8220;unit of account&amp;#8221; concept when we receive consideration under a collaboration to determine when we recognize revenue or a contra expense&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;3)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 72pt;"&gt;&lt;/td&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&amp;#9679;&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we will not recognize revenue for the transaction&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The updated guidance is effective for public entities for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. Early adoption is permitted. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it will have on our condensed consolidated financial statements and disclosures.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:SignificantAccountingPoliciesTextBlock>
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font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;326&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(531&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;869,278&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by U.S. government agencies&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;124,744&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;71&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(15&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;124,800&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;328,340&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;110&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(12&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;328,438&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;63,366&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;10&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(203&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;63,173&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Other municipal debt securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,931&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,932&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: 13.5pt; margin-left: 4.5pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total securities with a maturity of one year or less&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,388,864&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;518&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(761&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,388,621&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Corporate debt securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;360,976&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,236&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(336&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;361,876&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by U.S. government agencies&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;120,341&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;279&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(112&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;120,508&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by the U.S. Treasury&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;33,569&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;12&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(22&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;33,559&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;15,615&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; 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vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;15,490&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: 13.5pt; margin-left: 4.5pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total securities with a maturity of more than one year&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;530,501&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,527&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(595&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;531,433&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total available-for-sale securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,919,365&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; 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font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1,356&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total equity securities included in other current assets (3)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; 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font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;968&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total available-for-sale and equity securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,920,577&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2,045&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1,600&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,921,022&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&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%;"&gt;&lt;tr&gt;&lt;td rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;/td&gt;&lt;td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" rowspan="1" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" rowspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Gross Unrealized&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" rowspan="1" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" rowspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;December 31, 2018&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" rowspan="1" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; 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text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Available-for-sale securities:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Corporate debt securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; 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width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(109&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;107,874&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by the U.S. Treasury&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;15,600&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(24&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;15,576&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;16,980&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(287&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;16,693&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total securities with a maturity of more than one year&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;439,387&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;388&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1,706&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;438,069&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total available-for-sale securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,873,317&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;419&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(4,068&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,869,668&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Equity securities:&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; margin-left: 18pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total equity securities included in other current assets (3)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,212&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;137&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#8212;&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,349&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Total available-for-sale and equity securities&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,874,529&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;556&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(4,068&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1,871,017&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our available-for-sale securities are held at amortized cost.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(2)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Includes investments classified as cash equivalents on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(3)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize our equity securities at 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 on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock>
  <!--Use of Estimates, Policy [Policy Text Block]-->
  <us-gaap:UseOfEstimates contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&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="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The preparation of condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States requires 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 those estimates.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:UseOfEstimates>
  <!--Shares used in computing basic net income (loss) per share (in shares)-->
  <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic contextRef="c20180101to20180331" unitRef="U001" decimals="-3">125330000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
  <!--Shares used in computing basic net income (loss) per share (in shares)-->
  <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic contextRef="c20190101to20190331" unitRef="U001" decimals="-3">138582000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
  <!--Shares used in computing diluted net income (loss) per share (in shares)-->
  <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding contextRef="c20190101to20190331" unitRef="U001" decimals="-3">141537000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
  <!--Shares used in computing diluted net income (loss) per share (in shares)-->
  <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding contextRef="c20180101to20180331" unitRef="U001" decimals="-3">125330000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
  <!--Long-term Obligations, Noncurrent-->
  <ions:LongTermObligationsNoncurrent contextRef="c20181231" unitRef="U002" decimals="-3">4914000</ions:LongTermObligationsNoncurrent>
  <!--Long-term Obligations, Noncurrent-->
  <ions:LongTermObligationsNoncurrent contextRef="c20190331" unitRef="U002" decimals="-3">16305000</ions:LongTermObligationsNoncurrent>
  <!--Cash, Cash Equivalents and Investments [Policy Text Block]-->
  <ions:CashCashEquivalentsAndInvestmentsPolicyTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cash, cash equivalents and investments&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &amp;#8220;available-for-sale&amp;#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments. We use the specific identification method to determine the cost of securities sold.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At March 31, 2019, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in four privately-held companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</ions:CashCashEquivalentsAndInvestmentsPolicyTextBlock>
  <!--Number of Privately-Held Companies in which Entity has Equity Investment-->
  <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment contextRef="c20190331" unitRef="U007" decimals="INF">4</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
  <!--Number of Publicly-Held Companies in which Entity has Equity Investment-->
  <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment contextRef="c20190331" unitRef="U007" decimals="INF">2</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
  <!--Available-for-sale Securities, Debt Maturities, within One Year, Percentage-->
  <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage contextRef="c20190331" unitRef="U003" decimals="2">0.74</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage>
  <!--Available-for-sale Securities, Debt Maturities, within Two Years, Percentage-->
  <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage contextRef="c20190331" unitRef="U003" decimals="2">0.95</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage>
  <!--Available-for-sale Securities, Debt Maturities, Total, Percentage-->
  <ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage contextRef="c20190331" unitRef="U003" decimals="INF">1</ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage>
  <!--Available-for-sale Securities, Debt Maturities, after One Through Two Years, Percentage-->
  <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage contextRef="c20190331" unitRef="U003" decimals="2">0.21</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage>
  <!--Available-for-sale Securities, Debt Maturities, after Two Through Three Years, Percentage-->
  <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage contextRef="c20190331" unitRef="U003" decimals="2">0.05</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage>
  <!--Maximum contract maturity period, range 1-->
  <ions:MaximumContractMaturityPeriodRange1 contextRef="c20190101to20190331">P1Y</ions:MaximumContractMaturityPeriodRange1>
  <!--Maximum contract maturity period, range 2-->
  <ions:MaximumContractMaturityPeriodRange2 contextRef="c20190101to20190331">P2Y</ions:MaximumContractMaturityPeriodRange2>
  <!--Maximum contract maturity period, range 3-->
  <ions:MaximumContractMaturityPeriodRange3 contextRef="c20190101to20190331">P3Y</ions:MaximumContractMaturityPeriodRange3>
  <!--Research, Development and Patent Expense-->
  <ions:ResearchDevelopmentAndPatentExpense contextRef="c20180101to20180331" unitRef="U002" decimals="-3">104067000</ions:ResearchDevelopmentAndPatentExpense>
  <!--Research, Development and Patent Expense-->
  <ions:ResearchDevelopmentAndPatentExpense contextRef="c20190101to20190331" unitRef="U002" decimals="-3">106417000</ions:ResearchDevelopmentAndPatentExpense>
  <!--Non-cash Capital and Patent Expenditures-->
  <ions:NonCashCapitalAndPatentExpenditures contextRef="c20190101to20190331" unitRef="U002" decimals="-3">1864000</ions:NonCashCapitalAndPatentExpenditures>
  <!--Non-cash Capital and Patent Expenditures-->
  <ions:NonCashCapitalAndPatentExpenditures contextRef="c20180101to20180331" unitRef="U002" decimals="-3">2091000</ions:NonCashCapitalAndPatentExpenditures>
  <!--Increase (Decrease) in Accrued and Deferred Liabilities-->
  <ions:IncreaseDecreaseInAccruedAndDeferredLiabilities contextRef="c20180101to20180331" unitRef="U002" decimals="-3">-1695000</ions:IncreaseDecreaseInAccruedAndDeferredLiabilities>
  <!--Increase (Decrease) in Accrued and Deferred Liabilities-->
  <ions:IncreaseDecreaseInAccruedAndDeferredLiabilities contextRef="c20190101to20190331" unitRef="U002" decimals="-3">13756000</ions:IncreaseDecreaseInAccruedAndDeferredLiabilities>
  <!--Payments to Acquire Licenses and Other Assets-->
  <ions:PaymentsToAcquireLicensesAndOtherAssets contextRef="c20180101to20180331" unitRef="U002" decimals="-3">738000</ions:PaymentsToAcquireLicensesAndOtherAssets>
  <!--Payments to Acquire Licenses and Other Assets-->
  <ions:PaymentsToAcquireLicensesAndOtherAssets contextRef="c20190101to20190331" unitRef="U002" decimals="-3">1032000</ions:PaymentsToAcquireLicensesAndOtherAssets>
  <!--Debt Securities, Available-for-sale and Equity Securities, FV-NI, Cost-->
  <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost contextRef="c20190331" unitRef="U002" decimals="-3">1920577000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost>
  <!--Debt Securities, Available-for-sale and Equity Securities, FV-NI, Cost-->
  <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost contextRef="c20181231" unitRef="U002" decimals="-3">1874529000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost>
  <!--Debt Securities, Available-for-sale and Equity Securities, FV-NI-->
  <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI contextRef="c20181231" unitRef="U002" decimals="-3">1871017000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI>
  <!--Debt Securities, Available-for-sale and Equity Securities, FV-NI-->
  <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI contextRef="c20190331" unitRef="U002" decimals="-3">1921022000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI>
  <!--Debt Securities, Available-for-sale and Equity Securities, FV-NI, Gross Unrealized Gain-->
  <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain contextRef="c20190331" unitRef="U002" decimals="-3">2045000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain>
  <!--Debt Securities, Available-for-sale and Equity Securities, FV-NI, Gross Unrealized Gain-->
  <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain contextRef="c20181231" unitRef="U002" decimals="-3">556000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain>
  <!--Debt Securities, Available-for-sale and Equity Securities, FV-NI, Gross Unrealized Loss-->
  <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss contextRef="c20181231" unitRef="U002" decimals="-3">4068000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss>
  <!--Debt Securities, Available-for-sale and Equity Securities, FV-NI, Gross Unrealized Loss-->
  <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss contextRef="c20190331" unitRef="U002" decimals="-3">1600000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss>
  <!--Number of agreements with collaboration partner-Biogen Inc. [Member]-->
  <ions:NumberOfAgreementsWithCollaborationPartner contextRef="c20180401to20180630_MajorCustomersAxis_BiogenIncMember" unitRef="U006" decimals="INF">2</ions:NumberOfAgreementsWithCollaborationPartner>
  <!--Upfront payment received-Collaborative Arrangement and Licensing Agreement Entered Into in May 2015 with Bayer [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20150501to20150531_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" decimals="-6">100000000</ions:UpfrontPaymentReceived>
  <!--Upfront payment received-Collaborative Arrangement and Licensing Agreement Amended in February 2017 with Bayer [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20170201to20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U002" decimals="-6">75000000</ions:UpfrontPaymentReceived>
  <!--Upfront payment received-Collaborative Arrangement and Licensing Agreement Entered Into in October 2018 with Roche [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U002" decimals="-6">75000000</ions:UpfrontPaymentReceived>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangements and Licensing Agreements, Bayer [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20170228_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember" unitRef="U005" decimals="INF">3</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of performance obligations at inception of contract-->
  <ions:RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract contextRef="c20190101to20190331" unitRef="U005" decimals="INF">1</ions:RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract>
  <!--Revenue from Contract with Customer, Transaction Price, Additions-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPriceAdditions contextRef="c20170701to20170930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-6">10000000</ions:RevenueFromContractWithCustomerTransactionPriceAdditions>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Amended in February 2017 with Bayer [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U002" decimals="-6">75000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Cumulative Cost of Products Sold-->
  <ions:CumulativeCostOfProductsSold contextRef="c20190331" unitRef="U002" decimals="-5">300000</ions:CumulativeCostOfProductsSold>
  <!--Incremental Common Shares Attributable to Employee Stock Purchase Plan-->
  <ions:IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan contextRef="c20190101to20190331" unitRef="U001" decimals="-3">38000</ions:IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan>
  <!--Weighted average number of shares owned in subsidiary-Akcea Therapeutics, Inc. [Member]-Common Stock [Member]-->
  <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary contextRef="c20180101to20180331_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-3">45448000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
  <!--Weighted average number of shares owned in subsidiary-Common Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary contextRef="c20190101to20190331_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-3">68582000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
  <!--Receipt of shares in subsidiary-Akcea Therapeutics, Inc. [Member]-->
  <ions:ReceiptOfSharesInSubsidiary contextRef="c20190101to20190331_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5">2800000</ions:ReceiptOfSharesInSubsidiary>
  <!--Receipt of shares in subsidiary-Akcea Therapeutics, Inc. [Member]-->
  <ions:ReceiptOfSharesInSubsidiary contextRef="c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5">2800000</ions:ReceiptOfSharesInSubsidiary>
  <!--Cumulative payments received-Collaborative Arrangements and Licensing Agreements, Biogen [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20190331_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-8">2100000000</ions:CumulativePaymentsReceived>
  <!--Cumulative payments received-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6">220000000</ions:CumulativePaymentsReceived>
  <!--Cumulative payments received-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-Minimum [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20190331_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">330000000</ions:CumulativePaymentsReceived>
  <!--Sublicense fee paid for license of drug-Akcea Therapeutics, Inc. [Member]-->
  <ions:SublicenseFeePaidForLicenseOfDrug contextRef="c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-6">75000000</ions:SublicenseFeePaidForLicenseOfDrug>
  <!--Number of collaboration agreements-Collaborative Arrangement and Licensing Agreement Entered Into in October 2018 with Roche [Member]-->
  <ions:NumberOfCollaborationAgreements contextRef="c20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U006" decimals="INF">1</ions:NumberOfCollaborationAgreements>
  <!--Number of collaboration agreements-Collaborative Arrangements and Licensing Agreements, Roche [Member]-->
  <ions:NumberOfCollaborationAgreements contextRef="c20190331_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U006" decimals="INF">2</ions:NumberOfCollaborationAgreements>
  <!--Number of collaboration agreements-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:NumberOfCollaborationAgreements contextRef="c20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U006" decimals="INF">1</ions:NumberOfCollaborationAgreements>
  <!--Next potential milestone payment-Subsequent Event [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]-->
  <ions:NextPotentialMilestonePayment contextRef="c20190430_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-6">10000000</ions:NextPotentialMilestonePayment>
  <!--Next potential milestone payment-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:NextPotentialMilestonePayment contextRef="c20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6">15000000</ions:NextPotentialMilestonePayment>
  <!--Milestone payments received-Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]-Subsequent Event [Member]-->
  <ions:MilestonePaymentsReceived contextRef="c20190401to20190430_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-5">7500000</ions:MilestonePaymentsReceived>
  <!--Upfront payment received, including purchase of stock-Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]-->
  <ions:UpfrontPaymentReceivedIncludingPurchaseOfStock contextRef="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-9">1000000000</ions:UpfrontPaymentReceivedIncludingPurchaseOfStock>
  <!--Number of additional drugs in clinical development to treat neurodegenerative diseases-Collaborative Arrangements and Licensing Agreements, Biogen [Member]-->
  <ions:NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases contextRef="c20190331_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U012" decimals="INF">6</ions:NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases>
  <!--Period after billing when payment is received-->
  <ions:PeriodAfterBillingWhenPaymentIsReceived contextRef="c20190101to20190331">P3M</ions:PeriodAfterBillingWhenPaymentIsReceived>
  <!--Lessee, Operating Lease, Period of Free Rent-Office Space for Corporate Headquarters [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:LesseeOperatingLeasePeriodOfFreeRent contextRef="c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember">P3M</ions:LesseeOperatingLeasePeriodOfFreeRent>
  <!--Lessee, Operating Lease, Allowance for Tenant Improvements-Akcea Therapeutics, Inc. [Member]-Office Space for Corporate Headquarters [Member]-->
  <ions:LesseeOperatingLeaseAllowanceForTenantImprovements contextRef="c20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember" unitRef="U002" decimals="-5">3800000</ions:LesseeOperatingLeaseAllowanceForTenantImprovements>
  <!--Lessee, Leasing Arrangements, Operating Leases, Number of options to extend lease-Office Space Subleased to Akcea Therapeutics, Inc. [Member]-->
  <ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease contextRef="c20190101to20190331_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" unitRef="U010" decimals="INF">1</ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease>
  <!--Lessee, Leasing Arrangements, Operating Leases, Number of options to extend lease-Office and Laboratory Space Adjacent to Manufacturing Facility [Member]-->
  <ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease contextRef="c20190101to20190331_PropertyPlantAndEquipmentByTypeAxis_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" unitRef="U010" decimals="INF">2</ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease>
  <!--Lessee, Operating Lease, Letter of Credit to Secure Lease Obligation on Third Anniversary of Rent Commencement Date-Akcea Therapeutics, Inc. [Member]-Office Space for Corporate Headquarters [Member]-->
  <ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate contextRef="c20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember" unitRef="U002" decimals="-5">1800000</ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate>
  <!--Lessee, Operating Lease, Initial Letter of Credit to Secure Lease Obligation-Office Space for Corporate Headquarters [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation contextRef="c20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember" unitRef="U002" decimals="-5">2400000</ions:LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation>
  <!--Lessee, Operating Lease, Letter of Credit to Secure Lease Obligation on Fifth Anniversary of Rent Commencement Date-Akcea Therapeutics, Inc. [Member]-Office Space for Corporate Headquarters [Member]-->
  <ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate contextRef="c20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember" unitRef="U002" decimals="-5">1200000</ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate>
  <!--Lessee, Operating Lease Information [Table Text Block]-->
  <ions:LesseeOperatingLeaseInformationTableTextBlock contextRef="c20190101to20190331">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts related to our operating leases were as follows (dollar amounts in millions):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"&gt;&lt;div style="text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;At March 31, 2019&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Right-of-use operating lease assets (1)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;13.1&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Operating lease liabilities (2)&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;18.0&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Weighted average remaining lease term&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"&gt;&lt;div style="text-align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;9 years&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Weighted average discount rate&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;7.6&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;%&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(1)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Included in deposits and other assets on our condensed consolidated balance sheet.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&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%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(2)&lt;/font&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Current portion of $2.0 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</ions:LesseeOperatingLeaseInformationTableTextBlock>
  <!--Number of income tax expense components-->
  <ions:NumberOfIncomeTaxExpenseComponents contextRef="c20190101to20190331" unitRef="U011" decimals="INF">2</ions:NumberOfIncomeTaxExpenseComponents>
  <link:footnoteLink xlink:role="http://www.xbrl.org/2003/role/link" xlink:type="extended">
    <link:footnote xlink:label="Footnote-Item-1" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Included in short-term investments on our condensed consolidated balance sheet.</link:footnote>
    <link:loc xlink:href="#Item-1" xlink:label="Item-1_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-1_lbl" xlink:to="Footnote-Item-1" xlink:type="arc" />
    <link:loc xlink:href="#Item-7" xlink:label="Item-7_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-7_lbl" xlink:to="Footnote-Item-1" xlink:type="arc" />
    <link:loc xlink:href="#Item-8" xlink:label="Item-8_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-8_lbl" xlink:to="Footnote-Item-1" xlink:type="arc" />
    <link:loc xlink:href="#Item-9" xlink:label="Item-9_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-9_lbl" xlink:to="Footnote-Item-1" xlink:type="arc" />
    <link:loc xlink:href="#Item-10" xlink:label="Item-10_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-10_lbl" xlink:to="Footnote-Item-1" xlink:type="arc" />
    <link:footnote xlink:label="Footnote-Item-2" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">$50.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</link:footnote>
    <link:loc xlink:href="#Item-2" xlink:label="Item-2_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-2_lbl" xlink:to="Footnote-Item-2" xlink:type="arc" />
    <link:footnote xlink:label="Footnote-Item-3" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">$15.0 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</link:footnote>
    <link:loc xlink:href="#Item-3" xlink:label="Item-3_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-3_lbl" xlink:to="Footnote-Item-3" xlink:type="arc" />
    <link:footnote xlink:label="Footnote-Item-4" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">$27.1 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</link:footnote>
    <link:loc xlink:href="#Item-4" xlink:label="Item-4_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-4_lbl" xlink:to="Footnote-Item-4" xlink:type="arc" />
    <link:loc xlink:href="#Item-5" xlink:label="Item-5_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-5_lbl" xlink:to="Footnote-Item-4" xlink:type="arc" />
    <link:footnote xlink:label="Footnote-Item-5" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">$14.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</link:footnote>
    <link:loc xlink:href="#Item-6" xlink:label="Item-6_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-6_lbl" xlink:to="Footnote-Item-5" xlink:type="arc" />
    <link:footnote xlink:label="Footnote-Item-6" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Our available-for-sale securities are held at amortized cost.</link:footnote>
    <link:loc xlink:href="#Item-11" xlink:label="Item-11_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-11_lbl" xlink:to="Footnote-Item-6" xlink:type="arc" />
    <link:loc xlink:href="#Item-12" xlink:label="Item-12_lbl" xlink:type="locator" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-12_lbl" xlink:to="Footnote-Item-6" xlink:type="arc" />
    <link:loc xlink:href="#Item-13" xlink:label="Item-13_lbl" xlink:type="locator" />
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</xs:schema>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.CAL
<SEQUENCE>7
<FILENAME>ions-20190331_cal.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION CALCULATION LINKBASE
<TEXT>
<XBRL>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractReceivablesAbstract" xlink:to="us-gaap_ContractReceivablesAbstract_lbl1" xlink:title="label: ContractReceivablesAbstract to us-gaap_ContractReceivablesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:label="ContractWithCustomerLiability" xlink:title="ContractWithCustomerLiability" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiability_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl">Deferred revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability_lbl" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiability_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl1">Contract with Customer, Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability_lbl1" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContractWithCustomerAssetNetCurrent" xlink:label="ContractWithCustomerAssetNetCurrent" xlink:title="ContractWithCustomerAssetNetCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerAssetNetCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerAssetNetCurrent_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerAssetNetCurrent_lbl">Contracts receivable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerAssetNetCurrent" xlink:to="us-gaap_ContractWithCustomerAssetNetCurrent_lbl" xlink:title="label: ContractWithCustomerAssetNetCurrent to us-gaap_ContractWithCustomerAssetNetCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1">Contract with Customer, Asset, Net, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerAssetNetCurrent" xlink:to="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" xlink:title="label: ContractWithCustomerAssetNetCurrent to us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="ContractWithCustomerLiabilityCurrent" xlink:title="ContractWithCustomerLiabilityCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl">Current portion of deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1">Contract with Customer, Liability, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ConvertiblePreferredStockMember" xlink:label="ConvertiblePreferredStockMember" xlink:title="ConvertiblePreferredStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertiblePreferredStockMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertiblePreferredStockMember_lbl" xml:lang="en-US" id="us-gaap_ConvertiblePreferredStockMember_lbl">Preferred Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertiblePreferredStockMember" xlink:to="us-gaap_ConvertiblePreferredStockMember_lbl" xlink:title="label: ConvertiblePreferredStockMember to us-gaap_ConvertiblePreferredStockMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertiblePreferredStockMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertiblePreferredStockMember_lbl1" xml:lang="en-US" id="us-gaap_ConvertiblePreferredStockMember_lbl1">Convertible Preferred Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertiblePreferredStockMember" xlink:to="us-gaap_ConvertiblePreferredStockMember_lbl1" xlink:title="label: ConvertiblePreferredStockMember to us-gaap_ConvertiblePreferredStockMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ConvertibleDebtNoncurrent" xlink:label="ConvertibleDebtNoncurrent" xlink:title="ConvertibleDebtNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtNoncurrent_lbl" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent_lbl">1 percent convertible senior notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent_lbl1">Convertible Debt, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CorporateDebtSecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CorporateDebtSecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_CorporateDebtSecuritiesMember_lbl">Corporate Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CorporateDebtSecuritiesMember" xlink:to="us-gaap_CorporateDebtSecuritiesMember_lbl" xlink:title="label: CorporateDebtSecuritiesMember to us-gaap_CorporateDebtSecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CorporateDebtSecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CorporateDebtSecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_CorporateDebtSecuritiesMember_lbl1">Corporate Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CorporateDebtSecuritiesMember" xlink:to="us-gaap_CorporateDebtSecuritiesMember_lbl1" xlink:title="label: CorporateDebtSecuritiesMember to us-gaap_CorporateDebtSecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CostOfGoodsAndServicesSoldAbstract" xlink:label="CostOfGoodsAndServicesSoldAbstract" xlink:title="CostOfGoodsAndServicesSoldAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl">Cost of Products Sold [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSoldAbstract" xlink:to="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl" xlink:title="label: CostOfGoodsAndServicesSoldAbstract to us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl1" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl1">Cost of Goods and Services Sold [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSoldAbstract" xlink:to="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl1" xlink:title="label: CostOfGoodsAndServicesSoldAbstract to us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="CostOfGoodsAndServicesSold" xlink:title="CostOfGoodsAndServicesSold" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfGoodsAndServicesSold_lbl" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold_lbl">Cost of products 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_lbl" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfGoodsAndServicesSold_lbl1" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold_lbl1">Cost of Goods and Services Sold</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSold" xlink:to="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CostOfSalesPolicyTextBlock" xlink:label="CostOfSalesPolicyTextBlock" xlink:title="CostOfSalesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfSalesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_CostOfSalesPolicyTextBlock_lbl">Cost of Products Sold</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock_lbl" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesPolicyTextBlock_lbl1">Cost of Sales, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CostOfSalesMember" xlink:label="CostOfSalesMember" xlink:title="CostOfSalesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfSalesMember_lbl" xml:lang="en-US" id="us-gaap_CostOfSalesMember_lbl">Cost of Products Sold [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember_lbl" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesMember_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesMember_lbl1">Cost of Sales [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember_lbl1" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl">Expenses:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl1">Costs and Expenses [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CostsAndExpenses" xlink:label="CostsAndExpenses" xlink:title="CostsAndExpenses" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_CostsAndExpenses_lbl" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl">Total operating expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_CostsAndExpenses_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl1">Total operating expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl1" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpenses_lbl2" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl2">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_lbl2" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CustomerConcentrationRiskMember" xlink:label="CustomerConcentrationRiskMember" xlink:title="CustomerConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CustomerConcentrationRiskMember_lbl" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember_lbl">Strategic Partner [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CustomerConcentrationRiskMember" xlink:to="us-gaap_CustomerConcentrationRiskMember_lbl" xlink:title="label: CustomerConcentrationRiskMember to us-gaap_CustomerConcentrationRiskMember_lbl" />
    <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="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="DisaggregationOfRevenueLineItems" xlink:title="DisaggregationOfRevenueLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DisaggregationOfRevenueLineItems_lbl" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueLineItems_lbl">Disaggregation of Revenue [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="us-gaap_DisaggregationOfRevenueLineItems_lbl" xlink:title="label: DisaggregationOfRevenueLineItems to us-gaap_DisaggregationOfRevenueLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="DisaggregationOfRevenueTable" xlink:title="DisaggregationOfRevenueTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DisaggregationOfRevenueTable_lbl" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueTable_lbl">Disaggregation of Revenue [Table]</link:label>
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    <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" />
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    <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="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:label="IncreaseDecreaseInStockholdersEquityRollForward" xlink:title="IncreaseDecreaseInStockholdersEquityRollForward" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" xlink:title="label: IncreaseDecreaseInStockholdersEquityRollForward to us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1">Increase (Decrease) in Stockholders' Equity [Roll Forward]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xlink:title="label: IncreaseDecreaseInStockholdersEquityRollForward to us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" xml:lang="en-US" id="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1">Intangible Assets, Finite-Lived, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IntangibleAssetsFiniteLivedPolicy" xlink:to="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" xlink:title="label: IntangibleAssetsFiniteLivedPolicy to us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_InterestExpense" xlink:label="InterestExpense" xlink:title="InterestExpense" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpense" xlink:to="us-gaap_InterestExpense_lbl" xlink:title="label: InterestExpense to us-gaap_InterestExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestExpense_lbl1" xml:lang="en-US" id="us-gaap_InterestExpense_lbl1">Interest Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpense" xlink:to="us-gaap_InterestExpense_lbl1" xlink:title="label: InterestExpense to us-gaap_InterestExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_InterestPaidNet" xlink:label="InterestPaidNet" xlink:title="InterestPaidNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InterestPaidNet_lbl" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl">Interest paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestPaidNet_lbl1" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl1">Interest Paid, Excluding Capitalized Interest, Operating Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl1" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWriteDown" xlink:to="us-gaap_InventoryWriteDown_lbl" xlink:title="label: InventoryWriteDown to us-gaap_InventoryWriteDown_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWriteDown" xlink:to="us-gaap_InventoryWriteDown_lbl1" xlink:title="label: InventoryWriteDown to us-gaap_InventoryWriteDown_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeasesTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeasesTextBlock_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeasesTextBlock_lbl">Operating Leases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasesTextBlock" xlink:to="us-gaap_LesseeOperatingLeasesTextBlock_lbl" xlink:title="label: LesseeOperatingLeasesTextBlock to us-gaap_LesseeOperatingLeasesTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeasesTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeasesTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeasesTextBlock_lbl1">Lessee, Operating Leases [Text Block]</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" />
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeOperatingLeaseTermOfContract" xlink:label="LesseeOperatingLeaseTermOfContract" xlink:title="LesseeOperatingLeaseTermOfContract" />
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeLeaseDescriptionLineItems" xlink:label="LesseeLeaseDescriptionLineItems" xlink:title="LesseeLeaseDescriptionLineItems" />
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:label="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:title="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" />
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1">Lessee, Operating Lease, Liability, Payments, Due Year Five</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeLeaseDescriptionTable" xlink:label="LesseeLeaseDescriptionTable" xlink:title="LesseeLeaseDescriptionTable" />
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl">Remainder of 2019</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1">Lessee, Operating Lease, Liability, Payments, Due Next Twelve Months</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm" xlink:label="LesseeOperatingLeaseRenewalTerm" xlink:title="LesseeOperatingLeaseRenewalTerm" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl">Term of lease extension</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseRenewalTerm" xlink:to="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xlink:title="label: LesseeOperatingLeaseRenewalTerm to us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1">Lessee, Operating Lease, Renewal Term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseRenewalTerm" xlink:to="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xlink:title="label: LesseeOperatingLeaseRenewalTerm to us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl">2021</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearThree to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1">Lessee, Operating Lease, Liability, Payments, Due Year Three</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearThree to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl">Thereafter</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1">Lessee, Operating Lease, Liability, Payments, Due after Year Five</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LeasesAbstract" xlink:label="LeasesAbstract" xlink:title="LeasesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LeasesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LeasesAbstract_lbl" xml:lang="en-US" id="us-gaap_LeasesAbstract_lbl">Operating Leases [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LeasesAbstract" xlink:to="us-gaap_LeasesAbstract_lbl" xlink:title="label: LeasesAbstract to us-gaap_LeasesAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl">LIABILITIES AND STOCKHOLDERS' EQUITY</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xlink:title="label: LiabilitiesAndStockholdersEquityAbstract to us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1">Liabilities and Equity [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xlink:title="label: LiabilitiesAndStockholdersEquityAbstract to us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_Liabilities" xlink:label="Liabilities" xlink:title="Liabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_Liabilities_lbl" xml:lang="en-US" id="us-gaap_Liabilities_lbl">Total liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities_lbl" xlink:title="label: Liabilities to us-gaap_Liabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Liabilities_lbl1" xml:lang="en-US" id="us-gaap_Liabilities_lbl1">Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities_lbl1" xlink:title="label: Liabilities to us-gaap_Liabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="LiabilitiesAndStockholdersEquity" xlink:title="LiabilitiesAndStockholdersEquity" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquity_lbl">Total liabilities and stockholders' equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xlink:title="label: LiabilitiesAndStockholdersEquity to us-gaap_LiabilitiesAndStockholdersEquity_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquity_lbl1">Liabilities and Equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xlink:title="label: LiabilitiesAndStockholdersEquity to us-gaap_LiabilitiesAndStockholdersEquity_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LiabilitiesCurrentAbstract" xlink:label="LiabilitiesCurrentAbstract" xlink:title="LiabilitiesCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesCurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesCurrentAbstract_lbl">Current liabilities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrentAbstract_lbl" xlink:title="label: LiabilitiesCurrentAbstract to us-gaap_LiabilitiesCurrentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesCurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesCurrentAbstract_lbl1">Liabilities, Current [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrentAbstract_lbl1" xlink:title="label: LiabilitiesCurrentAbstract to us-gaap_LiabilitiesCurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="LiabilitiesCurrent" xlink:title="LiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesCurrent_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent_lbl">Total current liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent_lbl" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent_lbl1">Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent_lbl1" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:label="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:title="LongTermDebtAndCapitalLeaseObligationsCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl">Current portion of long-term obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:to="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" xlink:title="label: LongTermDebtAndCapitalLeaseObligationsCurrent to us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1">Long-term Debt and Capital Lease Obligations, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:to="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" xlink:title="label: LongTermDebtAndCapitalLeaseObligationsCurrent to us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LongTermLoansFromBank" xlink:label="LongTermLoansFromBank" xlink:title="LongTermLoansFromBank" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermLoansFromBank_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermLoansFromBank_lbl" xml:lang="en-US" id="us-gaap_LongTermLoansFromBank_lbl">Long-term mortgage debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermLoansFromBank" xlink:to="us-gaap_LongTermLoansFromBank_lbl" xlink:title="label: LongTermLoansFromBank to us-gaap_LongTermLoansFromBank_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_MinorityInterest" xlink:label="MinorityInterest" xlink:title="MinorityInterest" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterest_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterest_lbl" xml:lang="en-US" id="us-gaap_MinorityInterest_lbl">Noncontrolling interest in Akcea Therapeutics, Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterest" xlink:to="us-gaap_MinorityInterest_lbl" xlink:title="label: MinorityInterest to us-gaap_MinorityInterest_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_MinorityInterestPeriodIncreaseDecrease" xlink:label="MinorityInterestPeriodIncreaseDecrease" xlink:title="MinorityInterestPeriodIncreaseDecrease" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl">Noncontrolling interest in Akcea Therapetuics, Inc.</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" xml:lang="en-US" id="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1">Noncontrolling Interest, Period Increase (Decrease)</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_MinorityInterestTable" xlink:label="MinorityInterestTable" xlink:title="MinorityInterestTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestTable_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestTable_lbl">Noncontrolling Interest [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestTable" xlink:to="us-gaap_MinorityInterestTable_lbl" xlink:title="label: MinorityInterestTable to us-gaap_MinorityInterestTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_MinorityInterestLineItems" xlink:label="MinorityInterestLineItems" xlink:title="MinorityInterestLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestLineItems_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestLineItems_lbl">Noncontrolling Interest [Line Items]</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="NonoperatingIncomeExpenseAbstract" xlink:title="NonoperatingIncomeExpenseAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NonoperatingIncomeExpenseAbstract_lbl" xml:lang="en-US" id="us-gaap_NonoperatingIncomeExpenseAbstract_lbl">Other income (expense):</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_NonoperatingIncomeExpenseAbstract_lbl" xlink:title="label: NonoperatingIncomeExpenseAbstract to us-gaap_NonoperatingIncomeExpenseAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xml:lang="en-US" id="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1">Nonoperating Income (Expense) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xlink:title="label: NonoperatingIncomeExpenseAbstract to us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NotesPayableFairValueDisclosure" xlink:label="NotesPayableFairValueDisclosure" xlink:title="NotesPayableFairValueDisclosure" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NotesPayableFairValueDisclosure_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NotesPayableFairValueDisclosure_lbl" xml:lang="en-US" id="us-gaap_NotesPayableFairValueDisclosure_lbl">Fair value of convertible notes</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_NotesPayableFairValueDisclosure_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NotesPayableFairValueDisclosure_lbl1" xml:lang="en-US" id="us-gaap_NotesPayableFairValueDisclosure_lbl1">Notes Payable, Fair Value Disclosure</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NotesPayableFairValueDisclosure" xlink:to="us-gaap_NotesPayableFairValueDisclosure_lbl1" xlink:title="label: NotesPayableFairValueDisclosure to us-gaap_NotesPayableFairValueDisclosure_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NumberOfReportableSegments" xlink:label="NumberOfReportableSegments" xlink:title="NumberOfReportableSegments" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfReportableSegments" xlink:to="us-gaap_NumberOfReportableSegments_lbl" xlink:title="label: NumberOfReportableSegments to us-gaap_NumberOfReportableSegments_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NoncontrollingInterestMember" xlink:label="NoncontrollingInterestMember" xlink:title="NoncontrollingInterestMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NoncontrollingInterestMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NoncontrollingInterestMember_lbl" xml:lang="en-US" id="us-gaap_NoncontrollingInterestMember_lbl">Noncontrolling Interest in Akcea Therapeutics, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NoncontrollingInterestMember" xlink:to="us-gaap_NoncontrollingInterestMember_lbl" xlink:title="label: NoncontrollingInterestMember to us-gaap_NoncontrollingInterestMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NoncontrollingInterestAbstract" xlink:label="NoncontrollingInterestAbstract" xlink:title="NoncontrollingInterestAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NoncontrollingInterestAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_NoncontrollingInterestAbstract_lbl" xml:lang="en-US" id="us-gaap_NoncontrollingInterestAbstract_lbl">Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NoncontrollingInterestAbstract" xlink:to="us-gaap_NoncontrollingInterestAbstract_lbl" xlink:title="label: NoncontrollingInterestAbstract to us-gaap_NoncontrollingInterestAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NoncontrollingInterestAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NoncontrollingInterestAbstract_lbl1" xml:lang="en-US" id="us-gaap_NoncontrollingInterestAbstract_lbl1">Noncontrolling Interest [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NoncontrollingInterestAbstract" xlink:to="us-gaap_NoncontrollingInterestAbstract_lbl1" xlink:title="label: NoncontrollingInterestAbstract to us-gaap_NoncontrollingInterestAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent" xlink:label="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:title="OperatingLeaseWeightedAverageDiscountRatePercent" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:to="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl" xlink:title="label: OperatingLeaseWeightedAverageDiscountRatePercent to us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1">Operating Lease, Weighted Average Discount Rate, Percent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:to="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" xlink:title="label: OperatingLeaseWeightedAverageDiscountRatePercent to us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="OperatingLeaseLiability" xlink:title="OperatingLeaseLiability" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiability_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiability_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseLiability_lbl">Total lease liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiability" xlink:to="us-gaap_OperatingLeaseLiability_lbl" xlink:title="label: OperatingLeaseLiability to us-gaap_OperatingLeaseLiability_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_OperatingLeaseLiability_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiability_lbl1">Operating lease liabilties</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiability_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiability_lbl2" xml:lang="en-US" id="us-gaap_OperatingLeaseLiability_lbl2">Operating Lease, Liability</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseRightOfUseAsset_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAsset_lbl">Right-of-use operating lease assets</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseRightOfUseAsset_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAsset_lbl1">Operating Lease, Right-of-Use Asset</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeaseExpense" xlink:label="OperatingLeaseExpense" xlink:title="OperatingLeaseExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseExpense_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseExpense_lbl">Rent expense</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeasePayments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeasePayments_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeasePayments_lbl1">Operating Lease, Payments</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="OperatingLeaseLiabilityCurrent" xlink:title="OperatingLeaseLiabilityCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiabilityCurrent_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityCurrent_lbl">Current portion of operating lease liabilties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilityCurrent" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent_lbl" xlink:title="label: OperatingLeaseLiabilityCurrent to us-gaap_OperatingLeaseLiabilityCurrent_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingIncomeLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_OperatingIncomeLoss_lbl1" xml:lang="en-US" id="us-gaap_OperatingIncomeLoss_lbl1">Income (loss) from operations</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ProductMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProductMember_lbl" xml:lang="en-US" id="us-gaap_ProductMember_lbl">TEGSEDI Product Sales, Net [Member]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProfitLoss" xlink:to="us-gaap_ProfitLoss_lbl1" xlink:title="label: ProfitLoss to us-gaap_ProfitLoss_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xlink:title="label: RevenueFromContractWithCustomerExcludingAssessedTax to us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" />
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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_lbl" xlink:title="label: StatementOfCashFlowsAbstract to us-gaap_StatementOfCashFlowsAbstract_lbl" />
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:label="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="StockIssuedDuringPeriodSharesShareBasedCompensation" />
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    <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" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl">Total stockholders' equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2">Balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl3" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl3" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquity" xlink:to="us-gaap_StockholdersEquity_lbl1" xlink:title="label: StockholdersEquity to us-gaap_StockholdersEquity_lbl1" />
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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_lbl" xlink:title="label: StockholdersEquityAbstract to us-gaap_StockholdersEquityAbstract_lbl" />
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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:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SupplementalCashFlowInformationAbstract" xlink:to="us-gaap_SupplementalCashFlowInformationAbstract_lbl1" xlink:title="label: SupplementalCashFlowInformationAbstract to us-gaap_SupplementalCashFlowInformationAbstract_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock" xlink:label="CashCashEquivalentsAndInvestmentsPolicyTextBlock" xlink:title="CashCashEquivalentsAndInvestmentsPolicyTextBlock" />
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaTherapeuticsIncMember_lbl" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl">Akcea Therapeutics, Inc. is a subsidiary of the Company and was formed to develop and commercialize drugs for cardiometabolic disorders.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" />
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    <link:label xlink:type="resource" xlink:label="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" xml:lang="en-US" id="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1">Number of Publicly-Held Companies in which Entity has Equity Investment</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" />
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" />
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2">After one year but within two years</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature beyond two years but within three 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="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, after Two Through Three Years, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl2">After two years but within three years</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange1" xlink:to="ions_MaximumContractMaturityPeriodRange1_lbl" xlink:title="label: MaximumContractMaturityPeriodRange1 to ions_MaximumContractMaturityPeriodRange1_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl1">Maximum contract maturity period, range 1</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange1" xlink:to="ions_MaximumContractMaturityPeriodRange1_lbl1" xlink:title="label: MaximumContractMaturityPeriodRange1 to ions_MaximumContractMaturityPeriodRange1_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl2" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl2">Maximum contract maturity period, range 1</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange1" xlink:to="ions_MaximumContractMaturityPeriodRange1_lbl2" xlink:title="label: MaximumContractMaturityPeriodRange1 to ions_MaximumContractMaturityPeriodRange1_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.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_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl2" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl2">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_lbl2" xlink:title="label: MaximumContractMaturityPeriodRange2 to ions_MaximumContractMaturityPeriodRange2_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.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_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange3_lbl2" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3_lbl2">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_lbl2" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_ConvertibleSeniorNotes1PercentMember" xlink:label="ConvertibleSeniorNotes1PercentMember" xlink:title="ConvertibleSeniorNotes1PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl">1 percent convertible senior notes due November 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl1">Convertible Senior Notes 1 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl2">1 Percent Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl3">1 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_ResearchDevelopmentAndPatentMember" xlink:label="ResearchDevelopmentAndPatentMember" xlink:title="ResearchDevelopmentAndPatentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl">Primary financial statement caption encompassing research, development and patent expenses.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl1" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl1">Research, Development and Patent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl1" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl2" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl2">Research, Development and Patent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl2" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_EquityIncentivePlan2011Member" xlink:label="EquityIncentivePlan2011Member" xlink:title="EquityIncentivePlan2011Member" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquityIncentivePlan2011Member_lbl" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member_lbl">Represents the stock option plan that provides for the issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to employees, directors, and consultants.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member_lbl" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquityIncentivePlan2011Member_lbl1" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member_lbl1">Equity Incentive Plan 2011 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member_lbl1" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquityIncentivePlan2011Member_lbl2" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member_lbl2">2011 Equity Incentive Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member_lbl2" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_BoardOfDirectorStockOptionMember" xlink:label="BoardOfDirectorStockOptionMember" xlink:title="BoardOfDirectorStockOptionMember" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BoardOfDirectorStockOptionMember_lbl" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember_lbl">An arrangement whereby a member of the Board of Directors is entitled to receive in the future, subject to vesting and other restrictions, a number of shares in the entity at a specified price, as defined in the agreement, as a form of compensation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember_lbl" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BoardOfDirectorStockOptionMember_lbl1" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember_lbl1">Board of Director Stock Option [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember_lbl1" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BoardOfDirectorStockOptionMember_lbl2" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember_lbl2">Board of Director Stock Options [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember_lbl2" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_BoardOfDirectorsMember" xlink:label="BoardOfDirectorsMember" xlink:title="BoardOfDirectorsMember" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BoardOfDirectorsMember_lbl" xml:lang="en-US" id="ions_BoardOfDirectorsMember_lbl">A group of individuals that are elected as, or elected to act as, representatives of the stockholders to establish corporate management related policies and to make decisions on major company issues.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorsMember" xlink:to="ions_BoardOfDirectorsMember_lbl" xlink:title="label: BoardOfDirectorsMember to ions_BoardOfDirectorsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BoardOfDirectorsMember_lbl1" xml:lang="en-US" id="ions_BoardOfDirectorsMember_lbl1">Board of Directors [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorsMember" xlink:to="ions_BoardOfDirectorsMember_lbl1" xlink:title="label: BoardOfDirectorsMember to ions_BoardOfDirectorsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_EmployeeMember" xlink:label="EmployeeMember" xlink:title="EmployeeMember" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EmployeeMember_lbl" xml:lang="en-US" id="ions_EmployeeMember_lbl">Persons hired to provide services to a company on a regular basis in exchange for compensation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeMember" xlink:to="ions_EmployeeMember_lbl" xlink:title="label: EmployeeMember to ions_EmployeeMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EmployeeMember_lbl1" xml:lang="en-US" id="ions_EmployeeMember_lbl1">Employee [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeMember" xlink:to="ions_EmployeeMember_lbl1" xlink:title="label: EmployeeMember to ions_EmployeeMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EmployeeMember_lbl2" xml:lang="en-US" id="ions_EmployeeMember_lbl2">Employees [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeMember" xlink:to="ions_EmployeeMember_lbl2" xlink:title="label: EmployeeMember to ions_EmployeeMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.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_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchDevelopmentAndPatentExpense_lbl2" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense_lbl2">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_lbl2" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CommercialMember" xlink:label="CommercialMember" xlink:title="CommercialMember" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CommercialMember_lbl1" xml:lang="en-US" id="ions_CommercialMember_lbl1">Commercial [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialMember" xlink:to="ions_CommercialMember_lbl1" xlink:title="label: CommercialMember to ions_CommercialMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CommercialMember_lbl2" xml:lang="en-US" id="ions_CommercialMember_lbl2">Commercial Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialMember" xlink:to="ions_CommercialMember_lbl2" xlink:title="label: CommercialMember to ions_CommercialMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_SPINRAZARoyaltiesMember" xlink:label="SPINRAZARoyaltiesMember" xlink:title="SPINRAZARoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_SPINRAZARoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SPINRAZARoyaltiesMember_lbl1" xml:lang="en-US" id="ions_SPINRAZARoyaltiesMember_lbl1">SPINRAZA Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SPINRAZARoyaltiesMember" xlink:to="ions_SPINRAZARoyaltiesMember_lbl1" xlink:title="label: SPINRAZARoyaltiesMember to ions_SPINRAZARoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SPINRAZARoyaltiesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SPINRAZARoyaltiesMember_lbl2" xml:lang="en-US" id="ions_SPINRAZARoyaltiesMember_lbl2">SPINRAZA Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SPINRAZARoyaltiesMember" xlink:to="ions_SPINRAZARoyaltiesMember_lbl2" xlink:title="label: SPINRAZARoyaltiesMember to ions_SPINRAZARoyaltiesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_LicensingAndOtherRoyaltiesMember" xlink:label="LicensingAndOtherRoyaltiesMember" xlink:title="LicensingAndOtherRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl1">Licensing and Other Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicensingAndOtherRoyaltiesMember" xlink:to="ions_LicensingAndOtherRoyaltiesMember_lbl1" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl2" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl2">Licensing and Other Royalty Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicensingAndOtherRoyaltiesMember" xlink:to="ions_LicensingAndOtherRoyaltiesMember_lbl2" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl3" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl3">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_lbl3" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1">Research and Development Revenue Under Collaborative Agreements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:to="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2">R&amp;D [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:to="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3">R&amp;D Revenue Under Collaborative Agreements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:to="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_GainLossOnExtinguishmentOfFinancingLiability" xlink:label="GainLossOnExtinguishmentOfFinancingLiability" xlink:title="GainLossOnExtinguishmentOfFinancingLiability" />
    <link:label xlink:type="resource" xlink:label="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl" xml:lang="en-US" id="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl">Difference between the purchase price of the facility and the carrying value of our financing liability at the time of the purchase.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnExtinguishmentOfFinancingLiability" xlink:to="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl" xlink:title="label: GainLossOnExtinguishmentOfFinancingLiability to ions_GainLossOnExtinguishmentOfFinancingLiability_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl1" xml:lang="en-US" id="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl1">Gain (Loss) on Extinguishment of Financing Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnExtinguishmentOfFinancingLiability" xlink:to="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl1" xlink:title="label: GainLossOnExtinguishmentOfFinancingLiability to ions_GainLossOnExtinguishmentOfFinancingLiability_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl2" xml:lang="en-US" id="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl2">Loss on extinguishment of financing liability for leased facility</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnExtinguishmentOfFinancingLiability" xlink:to="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl2" xlink:title="label: GainLossOnExtinguishmentOfFinancingLiability to ions_GainLossOnExtinguishmentOfFinancingLiability_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_NonCashCapitalAndPatentExpenditures" xlink:label="NonCashCapitalAndPatentExpenditures" xlink:title="NonCashCapitalAndPatentExpenditures" />
    <link:label xlink:type="resource" xlink:label="ions_NonCashCapitalAndPatentExpenditures_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NonCashCapitalAndPatentExpenditures_lbl" xml:lang="en-US" id="ions_NonCashCapitalAndPatentExpenditures_lbl">Future cash outflow to pay for purchases of fixed assets and patents that have been incurred.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonCashCapitalAndPatentExpenditures" xlink:to="ions_NonCashCapitalAndPatentExpenditures_lbl" xlink:title="label: NonCashCapitalAndPatentExpenditures to ions_NonCashCapitalAndPatentExpenditures_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NonCashCapitalAndPatentExpenditures_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NonCashCapitalAndPatentExpenditures_lbl1" xml:lang="en-US" id="ions_NonCashCapitalAndPatentExpenditures_lbl1">Non-cash Capital and Patent Expenditures</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonCashCapitalAndPatentExpenditures" xlink:to="ions_NonCashCapitalAndPatentExpenditures_lbl1" xlink:title="label: NonCashCapitalAndPatentExpenditures to ions_NonCashCapitalAndPatentExpenditures_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NonCashCapitalAndPatentExpenditures_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NonCashCapitalAndPatentExpenditures_lbl2" xml:lang="en-US" id="ions_NonCashCapitalAndPatentExpenditures_lbl2">Amounts accrued for capital and patent expenditures</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonCashCapitalAndPatentExpenditures" xlink:to="ions_NonCashCapitalAndPatentExpenditures_lbl2" xlink:title="label: NonCashCapitalAndPatentExpenditures to ions_NonCashCapitalAndPatentExpenditures_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:label="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:title="IncreaseDecreaseInAccruedAndDeferredLiabilities" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl" xml:lang="en-US" id="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl">The increase (decrease) during the reporting period in the aggregate amount of expenses incurred but not yet paid and deferred liabilities due within one year or operating cycle.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:to="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl" xlink:title="label: IncreaseDecreaseInAccruedAndDeferredLiabilities to ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl1" xml:lang="en-US" id="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl1">Increase (Decrease) in Accrued and Deferred Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:to="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl1" xlink:title="label: IncreaseDecreaseInAccruedAndDeferredLiabilities to ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl2" xml:lang="en-US" id="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl2">Accrued liabilities and deferred rent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:to="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl2" xlink:title="label: IncreaseDecreaseInAccruedAndDeferredLiabilities to ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_PaymentsToAcquireLicensesAndOtherAssets" xlink:label="PaymentsToAcquireLicensesAndOtherAssets" xlink:title="PaymentsToAcquireLicensesAndOtherAssets" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl" xml:lang="en-US" id="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl">The cash outflow for acquisition of licenses and other assets not otherwise defined in the taxonomy.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireLicensesAndOtherAssets" xlink:to="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl" xlink:title="label: PaymentsToAcquireLicensesAndOtherAssets to ions_PaymentsToAcquireLicensesAndOtherAssets_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl1" xml:lang="en-US" id="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl1">Payments to Acquire Licenses and Other Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireLicensesAndOtherAssets" xlink:to="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl1" xlink:title="label: PaymentsToAcquireLicensesAndOtherAssets to ions_PaymentsToAcquireLicensesAndOtherAssets_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl2" xml:lang="en-US" id="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl2">Acquisition of licenses and other assets, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireLicensesAndOtherAssets" xlink:to="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl2" xlink:title="label: PaymentsToAcquireLicensesAndOtherAssets to ions_PaymentsToAcquireLicensesAndOtherAssets_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_BiogenIncMember" xlink:label="BiogenIncMember" xlink:title="BiogenIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenIncMember_lbl" xml:lang="en-US" id="ions_BiogenIncMember_lbl">Biogen Inc. is an American multinational biotechnology company.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenIncMember" xlink:to="ions_BiogenIncMember_lbl" xlink:title="label: BiogenIncMember to ions_BiogenIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenIncMember_lbl1" xml:lang="en-US" id="ions_BiogenIncMember_lbl1">Biogen Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenIncMember" xlink:to="ions_BiogenIncMember_lbl1" xlink:title="label: BiogenIncMember to ions_BiogenIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenIncMember_lbl2" xml:lang="en-US" id="ions_BiogenIncMember_lbl2">Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenIncMember" xlink:to="ions_BiogenIncMember_lbl2" xlink:title="label: BiogenIncMember to ions_BiogenIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_NovartisInternationalAGMember" xlink:label="NovartisInternationalAGMember" xlink:title="NovartisInternationalAGMember" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisInternationalAGMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NovartisInternationalAGMember_lbl" xml:lang="en-US" id="ions_NovartisInternationalAGMember_lbl">Novartis International AG is a Swiss multinational pharmaceutical company based in Basel, Switzerland.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisInternationalAGMember" xlink:to="ions_NovartisInternationalAGMember_lbl" xlink:title="label: NovartisInternationalAGMember to ions_NovartisInternationalAGMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisInternationalAGMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NovartisInternationalAGMember_lbl1" xml:lang="en-US" id="ions_NovartisInternationalAGMember_lbl1">Novartis International AG [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisInternationalAGMember" xlink:to="ions_NovartisInternationalAGMember_lbl1" xlink:title="label: NovartisInternationalAGMember to ions_NovartisInternationalAGMember_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisInternationalAGMember" xlink:to="ions_NovartisInternationalAGMember_lbl2" xlink:title="label: NovartisInternationalAGMember to ions_NovartisInternationalAGMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.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-20190331.xsd#ions_SecuritiesWithMaturityOfOneYearOrLessMember" xlink:label="SecuritiesWithMaturityOfOneYearOrLessMember" xlink:title="SecuritiesWithMaturityOfOneYearOrLessMember" />
    <link:label xlink:type="resource" xlink:label="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl" xml:lang="en-US" id="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl">Represents investment securities with an expected maturity of one year or less.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl1" xml:lang="en-US" id="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl1">Securities with Maturity of One Year or Less [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecuritiesWithMaturityOfOneYearOrLessMember" xlink:to="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl1" xlink:title="label: SecuritiesWithMaturityOfOneYearOrLessMember to ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:label="SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:title="SecuritiesWithMaturityOfMoreThanOneYearMember" />
    <link:label xlink:type="resource" xlink:label="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl" xml:lang="en-US" id="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl">Represents investment securities with an expected maturity of more than one year.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:to="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl" xlink:title="label: SecuritiesWithMaturityOfMoreThanOneYearMember to ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl1" xml:lang="en-US" id="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl1">Securities with Maturity of More than One Year [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:to="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl1" xlink:title="label: SecuritiesWithMaturityOfMoreThanOneYearMember to ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl">Total of (1) amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) cost of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl1">Debt Securities, Available-for-sale and Equity Securities, FV-NI, Cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl2" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl2">Cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl2" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl">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).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl1">Debt Securities, Available-for-sale and Equity Securities, FV-NI</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl2" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI_lbl2">Estimated fair value</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl">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).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl1">Debt Securities, Available-for-sale and Equity Securities, FV-NI, Gross Unrealized Gain</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl2" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl2">Gross unrealized gains</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl2" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedGain_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl">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).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl1">Debt Securities, Available-for-sale and Equity Securities, FV-NI, Gross Unrealized Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl2" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl2">Gross unrealized losses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl2" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNIGrossUnrealizedLoss_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_NumberOfAgreementsWithCollaborationPartner" xlink:label="NumberOfAgreementsWithCollaborationPartner" xlink:title="NumberOfAgreementsWithCollaborationPartner" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl">The number of agreements entered into with the collaboration partner.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl1">Number of agreements with collaboration partner</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl2">Number of agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_UpfrontPaymentReceived" xlink:label="UpfrontPaymentReceived" xlink:title="UpfrontPaymentReceived" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontPaymentReceived_lbl" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl">The amount of upfront payments received during the period under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontPaymentReceived_lbl1" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl1">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl1" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontPaymentReceived_lbl2" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl2">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl2" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_HttMember" xlink:label="HttMember" xlink:title="HttMember" />
    <link:label xlink:type="resource" xlink:label="ions_HttMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_HttMember_lbl" xml:lang="en-US" id="ions_HttMember_lbl">An antisense drug targeting huntingtin, or HTT, protein.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="HttMember" xlink:to="ions_HttMember_lbl" xlink:title="label: HttMember to ions_HttMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_HttMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_HttMember_lbl1" xml:lang="en-US" id="ions_HttMember_lbl1">IONIS-HTT [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="HttMember" xlink:to="ions_HttMember_lbl1" xlink:title="label: HttMember to ions_HttMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.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>
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    <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-20190331.xsd#ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:label="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:title="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl">The number of performance obligations at the inception of a contract.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:label="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:title="RevenueFromContractWithCustomerTransactionPriceAdditions" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl">The additional amount of consideration the Company earned under the collaboration agreement that is added to the transaction price.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1">Revenue from Contract with Customer, Transaction Price, Additions</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:to="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" xlink:title="label: RevenueFromContractWithCustomerTransactionPriceAdditions to ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" />
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    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in October 2018 with Roche [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2">IONIS-FB-L for Complement-Mediated Diseases [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" />
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    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]</link:label>
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    <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" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Biogen Inc. in December 2012. This agreement is focused on developing and commercializing novel antisense drugs for up to three targets to treat neurological or neuromuscular diseases (Neurology).</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl">Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Bayer HealthCare.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBayerMember to ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1">Collaborative Arrangements and Licensing Agreements, Bayer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBayerMember to ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBayerMember to ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl">Represents information pertaining to collaborative arrangement with Bayer HealthCare amended in February 2017 to advance IONIS-FXIRx for the prevention of thrombosis and to initiate development of IONIS-FXI-LRx.</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl">Represents information pertaining to collaborative arrangement entered into with Bayer HealthCare in May 2015 to develop and commercialize IONIS-FXI for the prevention of thrombosis.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in May 2015 with Bayer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2">Bayer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CumulativeCostOfProductsSold" xlink:label="CumulativeCostOfProductsSold" xlink:title="CumulativeCostOfProductsSold" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativeCostOfProductsSold_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CumulativeCostOfProductsSold_lbl" xml:lang="en-US" id="ions_CumulativeCostOfProductsSold_lbl">The cumulative costs related to goods produced and sold that were previously recognized as expense.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_CumulativeCostOfProductsSold_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CumulativeCostOfProductsSold_lbl1" xml:lang="en-US" id="ions_CumulativeCostOfProductsSold_lbl1">Cumulative Cost of Products Sold</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativeCostOfProductsSold" xlink:to="ions_CumulativeCostOfProductsSold_lbl1" xlink:title="label: CumulativeCostOfProductsSold to ions_CumulativeCostOfProductsSold_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativeCostOfProductsSold_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CumulativeCostOfProductsSold_lbl2" xml:lang="en-US" id="ions_CumulativeCostOfProductsSold_lbl2">Costs incurred to produce TEGSEDI that were previously recognized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativeCostOfProductsSold" xlink:to="ions_CumulativeCostOfProductsSold_lbl2" xlink:title="label: CumulativeCostOfProductsSold to ions_CumulativeCostOfProductsSold_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_IonisCoreMember" xlink:label="IonisCoreMember" xlink:title="IonisCoreMember" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisCoreMember_lbl" xml:lang="en-US" id="ions_IonisCoreMember_lbl">Reportable segment in which the Company is exploiting a novel drug discovery platform created to generate a broad pipeline of first-in-class or best-in-class drugs for the Company and its partners. This segment generates revenue from a multifaceted partnering strategy. This strategy includes revenue from collaborations with preferred partners, traditional alliances and working with a consortium of companies that can exploit the Company's drugs and technology. Revenue from collaborations with preferred partners and traditional alliances may consist of upfront payments, milestone payments, licensing fees and royalties.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisCoreMember" xlink:to="ions_IonisCoreMember_lbl" xlink:title="label: IonisCoreMember to ions_IonisCoreMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IonisCoreMember_lbl1" xml:lang="en-US" id="ions_IonisCoreMember_lbl1">Ionis Core [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisCoreMember" xlink:to="ions_IonisCoreMember_lbl1" xlink:title="label: IonisCoreMember to ions_IonisCoreMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_IonisCoreMember_lbl2" xml:lang="en-US" id="ions_IonisCoreMember_lbl2">Ionis Core [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisCoreMember" xlink:to="ions_IonisCoreMember_lbl2" xlink:title="label: IonisCoreMember to ions_IonisCoreMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IonisCoreMember_lbl3" xml:lang="en-US" id="ions_IonisCoreMember_lbl3">Ionis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisCoreMember" xlink:to="ions_IonisCoreMember_lbl3" xlink:title="label: IonisCoreMember to ions_IonisCoreMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_AkceaTherapeuticsMember" xlink:label="AkceaTherapeuticsMember" xlink:title="AkceaTherapeuticsMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaTherapeuticsMember_lbl" xml:lang="en-US" id="ions_AkceaTherapeuticsMember_lbl">Reportable segment which includes the operations of the Company's wholly-owned subsidiary, Akcea Therapeutics, Inc., which was formed to develop and commercialize drugs for cardiometabolic disorders.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsMember" xlink:to="ions_AkceaTherapeuticsMember_lbl" xlink:title="label: AkceaTherapeuticsMember to ions_AkceaTherapeuticsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AkceaTherapeuticsMember_lbl1" xml:lang="en-US" id="ions_AkceaTherapeuticsMember_lbl1">Akcea Therapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsMember" xlink:to="ions_AkceaTherapeuticsMember_lbl1" xlink:title="label: AkceaTherapeuticsMember to ions_AkceaTherapeuticsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AkceaTherapeuticsMember_lbl2" xml:lang="en-US" id="ions_AkceaTherapeuticsMember_lbl2">Akcea Therapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsMember" xlink:to="ions_AkceaTherapeuticsMember_lbl2" xlink:title="label: AkceaTherapeuticsMember to ions_AkceaTherapeuticsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_DocumentAndEntityInformationAbstract" xlink:label="DocumentAndEntityInformationAbstract" xlink:title="DocumentAndEntityInformationAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_DocumentAndEntityInformationAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DocumentAndEntityInformationAbstract_lbl1" xml:lang="en-US" id="ions_DocumentAndEntityInformationAbstract_lbl1">Document and Entity Information [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentAndEntityInformationAbstract" xlink:to="ions_DocumentAndEntityInformationAbstract_lbl1" xlink:title="label: DocumentAndEntityInformationAbstract to ions_DocumentAndEntityInformationAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:label="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:title="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" />
    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl">Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of shares issuable related to employee stock purchase plan.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1">Incremental Common Shares Attributable to Employee Stock Purchase Plan</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2">Shares issuable related to our ESPP (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:label="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:title="WeightedAverageNumberOfSharesOwnedInSubsidiary" />
    <link:label xlink:type="resource" xlink:label="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" xml:lang="en-US" id="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl">Number of shares owned in the subsidiary during the reporting period determined by relating the portion of time within a reporting period that shares have been owned to the total time in that period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:to="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" xlink:title="label: WeightedAverageNumberOfSharesOwnedInSubsidiary to ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" xml:lang="en-US" id="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1">Weighted average number of shares owned in subsidiary</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:to="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" xlink:title="label: WeightedAverageNumberOfSharesOwnedInSubsidiary to ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" xml:lang="en-US" id="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2">Weighted average shares owned in Akcea (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:to="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" xlink:title="label: WeightedAverageNumberOfSharesOwnedInSubsidiary to ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_ReceiptOfSharesInSubsidiary" xlink:label="ReceiptOfSharesInSubsidiary" xlink:title="ReceiptOfSharesInSubsidiary" />
    <link:label xlink:type="resource" xlink:label="ions_ReceiptOfSharesInSubsidiary_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ReceiptOfSharesInSubsidiary_lbl" xml:lang="en-US" id="ions_ReceiptOfSharesInSubsidiary_lbl">The number of shares received from the subsidiary during the period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ReceiptOfSharesInSubsidiary" xlink:to="ions_ReceiptOfSharesInSubsidiary_lbl" xlink:title="label: ReceiptOfSharesInSubsidiary to ions_ReceiptOfSharesInSubsidiary_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ReceiptOfSharesInSubsidiary_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ReceiptOfSharesInSubsidiary_lbl1" xml:lang="en-US" id="ions_ReceiptOfSharesInSubsidiary_lbl1">Receipt of shares in subsidiary</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ReceiptOfSharesInSubsidiary" xlink:to="ions_ReceiptOfSharesInSubsidiary_lbl1" xlink:title="label: ReceiptOfSharesInSubsidiary to ions_ReceiptOfSharesInSubsidiary_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ReceiptOfSharesInSubsidiary_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ReceiptOfSharesInSubsidiary_lbl2" xml:lang="en-US" id="ions_ReceiptOfSharesInSubsidiary_lbl2">Additional shares of Akcea stock received (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ReceiptOfSharesInSubsidiary" xlink:to="ions_ReceiptOfSharesInSubsidiary_lbl2" xlink:title="label: ReceiptOfSharesInSubsidiary to ions_ReceiptOfSharesInSubsidiary_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CumulativePaymentsReceived" xlink:label="CumulativePaymentsReceived" xlink:title="CumulativePaymentsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CumulativePaymentsReceived_lbl" xml:lang="en-US" id="ions_CumulativePaymentsReceived_lbl">Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived_lbl" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CumulativePaymentsReceived_lbl1" xml:lang="en-US" id="ions_CumulativePaymentsReceived_lbl1">Cumulative payments received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived_lbl1" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CumulativePaymentsReceived_lbl2" xml:lang="en-US" id="ions_CumulativePaymentsReceived_lbl2">Cumulative payments received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived_lbl2" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_SublicenseFeePaidForLicenseOfDrug" xlink:label="SublicenseFeePaidForLicenseOfDrug" xlink:title="SublicenseFeePaidForLicenseOfDrug" />
    <link:label xlink:type="resource" xlink:label="ions_SublicenseFeePaidForLicenseOfDrug_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SublicenseFeePaidForLicenseOfDrug_lbl" xml:lang="en-US" id="ions_SublicenseFeePaidForLicenseOfDrug_lbl">The amount of the sublicense fee paid in common stock.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SublicenseFeePaidForLicenseOfDrug" xlink:to="ions_SublicenseFeePaidForLicenseOfDrug_lbl" xlink:title="label: SublicenseFeePaidForLicenseOfDrug to ions_SublicenseFeePaidForLicenseOfDrug_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SublicenseFeePaidForLicenseOfDrug_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SublicenseFeePaidForLicenseOfDrug_lbl1" xml:lang="en-US" id="ions_SublicenseFeePaidForLicenseOfDrug_lbl1">Sublicense fee paid for license of drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SublicenseFeePaidForLicenseOfDrug" xlink:to="ions_SublicenseFeePaidForLicenseOfDrug_lbl1" xlink:title="label: SublicenseFeePaidForLicenseOfDrug to ions_SublicenseFeePaidForLicenseOfDrug_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SublicenseFeePaidForLicenseOfDrug_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SublicenseFeePaidForLicenseOfDrug_lbl2" xml:lang="en-US" id="ions_SublicenseFeePaidForLicenseOfDrug_lbl2">Sublicense fee paid in stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SublicenseFeePaidForLicenseOfDrug" xlink:to="ions_SublicenseFeePaidForLicenseOfDrug_lbl2" xlink:title="label: SublicenseFeePaidForLicenseOfDrug to ions_SublicenseFeePaidForLicenseOfDrug_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.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-20190331.xsd#ions_AKCEAAPOALMember" xlink:label="AKCEAAPOALMember" xlink:title="AKCEAAPOALMember" />
    <link:label xlink:type="resource" xlink:label="ions_AKCEAAPOALMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AKCEAAPOALMember_lbl" xml:lang="en-US" id="ions_AKCEAAPOALMember_lbl">An antisense therapy with the potential to significantly reduce cardiovascular risk 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="AKCEAAPOALMember" xlink:to="ions_AKCEAAPOALMember_lbl" xlink:title="label: AKCEAAPOALMember to ions_AKCEAAPOALMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AKCEAAPOALMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AKCEAAPOALMember_lbl1" xml:lang="en-US" id="ions_AKCEAAPOALMember_lbl1">AKCEA-APO(a)-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AKCEAAPOALMember" xlink:to="ions_AKCEAAPOALMember_lbl1" xlink:title="label: AKCEAAPOALMember to ions_AKCEAAPOALMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AKCEAAPOALMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AKCEAAPOALMember_lbl2" xml:lang="en-US" id="ions_AKCEAAPOALMember_lbl2">AKCEA-APO(a)-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AKCEAAPOALMember" xlink:to="ions_AKCEAAPOALMember_lbl2" xlink:title="label: AKCEAAPOALMember to ions_AKCEAAPOALMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_RevenueFromContractWithCustomerBenchmarkMember" xlink:label="RevenueFromContractWithCustomerBenchmarkMember" xlink:title="RevenueFromContractWithCustomerBenchmarkMember" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl">Revenue from satisfaction of performance obligation by transferring promised product and service to customer, when it serves as benchmark in concentration of risk calculation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerBenchmarkMember" xlink:to="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl" xlink:title="label: RevenueFromContractWithCustomerBenchmarkMember to ions_RevenueFromContractWithCustomerBenchmarkMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl1">Revenue from Contract with Customer Benchmark [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerBenchmarkMember" xlink:to="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl1" xlink:title="label: RevenueFromContractWithCustomerBenchmarkMember to ions_RevenueFromContractWithCustomerBenchmarkMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl2">Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerBenchmarkMember" xlink:to="ions_RevenueFromContractWithCustomerBenchmarkMember_lbl2" xlink:title="label: RevenueFromContractWithCustomerBenchmarkMember to ions_RevenueFromContractWithCustomerBenchmarkMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_NumberOfCollaborationAgreements" xlink:label="NumberOfCollaborationAgreements" xlink:title="NumberOfCollaborationAgreements" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfCollaborationAgreements_lbl" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl">The number of collaboration agreements with the collaboration partner.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfCollaborationAgreements_lbl1" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl1">Number of collaboration agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl1" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfCollaborationAgreements_lbl2" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl2">Number of collaboration agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl2" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_NextPotentialMilestonePayment" xlink:label="NextPotentialMilestonePayment" xlink:title="NextPotentialMilestonePayment" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialMilestonePayment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NextPotentialMilestonePayment_lbl" xml:lang="en-US" id="ions_NextPotentialMilestonePayment_lbl">The next potential milestone payment to be earned under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialMilestonePayment" xlink:to="ions_NextPotentialMilestonePayment_lbl" xlink:title="label: NextPotentialMilestonePayment to ions_NextPotentialMilestonePayment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialMilestonePayment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NextPotentialMilestonePayment_lbl1" xml:lang="en-US" id="ions_NextPotentialMilestonePayment_lbl1">Next potential milestone payment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialMilestonePayment" xlink:to="ions_NextPotentialMilestonePayment_lbl1" xlink:title="label: NextPotentialMilestonePayment to ions_NextPotentialMilestonePayment_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialMilestonePayment_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NextPotentialMilestonePayment_lbl2" xml:lang="en-US" id="ions_NextPotentialMilestonePayment_lbl2">Next prospective milestone</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialMilestonePayment" xlink:to="ions_NextPotentialMilestonePayment_lbl2" xlink:title="label: NextPotentialMilestonePayment to ions_NextPotentialMilestonePayment_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsRocheMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl">Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsRocheMember to ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1">Collaborative Arrangements and Licensing Agreements, Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsRocheMember to ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2">Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsRocheMember to ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_MilestonePaymentsReceived" xlink:label="MilestonePaymentsReceived" xlink:title="MilestonePaymentsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MilestonePaymentsReceived_lbl" xml:lang="en-US" id="ions_MilestonePaymentsReceived_lbl">The amount of milestone 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="MilestonePaymentsReceived" xlink:to="ions_MilestonePaymentsReceived_lbl" xlink:title="label: MilestonePaymentsReceived to ions_MilestonePaymentsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MilestonePaymentsReceived_lbl1" xml:lang="en-US" id="ions_MilestonePaymentsReceived_lbl1">Milestone payments received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentsReceived" xlink:to="ions_MilestonePaymentsReceived_lbl1" xlink:title="label: MilestonePaymentsReceived to ions_MilestonePaymentsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_MilestonePaymentsReceived_lbl2" xml:lang="en-US" id="ions_MilestonePaymentsReceived_lbl2">Milestone payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentsReceived" xlink:to="ions_MilestonePaymentsReceived_lbl2" xlink:title="label: MilestonePaymentsReceived to ions_MilestonePaymentsReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl">Represents information pertaining to the expanded collaborative arrangement entered into with Biogen Inc. in April 2018 to develop novel antisense drug candidates for a broad range of neurological diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2">2018 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:label="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:title="UpfrontPaymentReceivedIncludingPurchaseOfStock" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" xml:lang="en-US" id="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl">The total amount of the upfront payment received, including the purchase of shares of the Company's stock, under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:to="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" xlink:title="label: UpfrontPaymentReceivedIncludingPurchaseOfStock to ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" xml:lang="en-US" id="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1">Upfront payment received, including purchase of stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:to="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" xlink:title="label: UpfrontPaymentReceivedIncludingPurchaseOfStock to ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" xml:lang="en-US" id="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:to="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" xlink:title="label: UpfrontPaymentReceivedIncludingPurchaseOfStock to ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl">Represents information pertaining to the collaborative arrangements and licensing 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="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1">Collaborative Arrangements and Licensing Agreements, Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2">Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases" xlink:label="NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases" xlink:title="NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl" xml:lang="en-US" id="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl">The number of additional drugs in clinical development to treat neurodegenerative diseases under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases" xlink:to="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl" xlink:title="label: NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases to ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl1" xml:lang="en-US" id="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl1">Number of additional drugs in clinical development to treat neurodegenerative diseases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases" xlink:to="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl1" xlink:title="label: NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases to ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl2" xml:lang="en-US" id="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl2">Number of additional drugs in clinical development to treat neurodegenerative diseases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases" xlink:to="ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl2" xlink:title="label: NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases to ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.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-20190331.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl">Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1">Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2">Collaborative Arrangements and Licensing Agreements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_PeriodAfterBillingWhenPaymentIsReceived" xlink:label="PeriodAfterBillingWhenPaymentIsReceived" xlink:title="PeriodAfterBillingWhenPaymentIsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl">The time period between billing a collaboration partner for goods delivered or services performed that are due unconditionally and payment is received from the collaboration partner, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1">Period after billing when payment is received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2">Period of time after billing when payment is received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_LesseeOperatingLeasePeriodOfFreeRent" xlink:label="LesseeOperatingLeasePeriodOfFreeRent" xlink:title="LesseeOperatingLeasePeriodOfFreeRent" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl">Period of time in which the rent is free under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1">Lessee, Operating Lease, Period of Free Rent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2">Period of free rent under lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:label="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:title="LesseeOperatingLeaseAllowanceForTenantImprovements" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl">Allowance for tenant improvements to the office space included in the lessee's operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:to="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" xlink:title="label: LesseeOperatingLeaseAllowanceForTenantImprovements to ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1">Lessee, Operating Lease, Allowance for Tenant Improvements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:to="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" xlink:title="label: LesseeOperatingLeaseAllowanceForTenantImprovements to ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2">Tenant improvement allowance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:to="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" xlink:title="label: LesseeOperatingLeaseAllowanceForTenantImprovements to ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:label="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:title="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" xml:lang="en-US" id="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl">The number of options to extend the lease under the lessee's operating leasing arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:to="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" xlink:title="label: LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease to ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" xml:lang="en-US" id="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1">Lessee, Leasing Arrangements, Operating Leases, Number of options to extend lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:to="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" xlink:title="label: LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease to ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" xml:lang="en-US" id="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2">Number of options to extend lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:to="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" xlink:title="label: LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease to ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:label="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:title="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl">Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the third anniversary of the rent commencement date.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1">Lessee, Operating Lease, Letter of Credit to Secure Lease Obligation on Third Anniversary of Rent Commencement Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2">Letter of credit on third anniversary of rent commencement date</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:label="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:title="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl">Initial letter of credit provided to lessor to secure lease obligation under lessee's operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:to="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" xlink:title="label: LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation to ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1">Lessee, Operating Lease, Initial Letter of Credit to Secure Lease Obligation</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:label="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:title="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1">Lessee, Operating Lease, Letter of Credit to Secure Lease Obligation on Fifth Anniversary of Rent Commencement Date</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_OfficeSpaceForCorporateHeadquartersMember" xlink:label="OfficeSpaceForCorporateHeadquartersMember" xlink:title="OfficeSpaceForCorporateHeadquartersMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20190331.xsd#ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:label="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:title="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:to="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl" xlink:title="label: OfficeSpaceSubleasedToAkceaTherapeuticsIncMember to ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl" />
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<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6833711456">
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<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">3 Months Ended</th>
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<th class="th"><div>Mar. 31, 2019</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="nump">140,322,994<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_DocumentType', window );">Document Type</a></td>
<td class="text">10-Q<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">Mar. 31,  2019<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">2019<span></span>
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<td class="text">Q1<span></span>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>If the value is true, then the document is an amendment to previously-filed/accepted document.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>This is focus fiscal period of the document report. For a first quarter 2006 quarterly report, which may also provide financial information from prior periods, the first fiscal quarter should be given as the fiscal period focus. Values: FY, Q1, Q2, Q3, Q4, H1, H2, M9, T1, T2, T3, M8, CY.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>This is focus fiscal year of the document report in CCYY 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>The end date of the period reflected on the cover page if a periodic report. For all other reports and registration statements containing historical data, it is the date up through which that historical data is presented.  If there is no historical data in the report, use the filing date. The format of the date is CCYY-MM-DD.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.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="top.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 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Indicate if registrant meets the emerging growth company criteria.</p></div>
<a href="javascript:void(0);" onclick="top.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 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Indicate if registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Securities Act<br> -Number 7A<br> -Section B<br> -Subsection 2<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Indicate whether the registrant is one of the following: (1) Large Accelerated Filer, (2) Accelerated Filer, (3) Non-accelerated Filer, (4) Smaller Reporting Company (Non-accelerated), (5) Smaller Reporting Accelerated Filer or (6) Smaller Reporting Company and Large 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="top.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 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.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="top.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 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Indicates that the company is a smaller reporting company with both a public float and revenues of less than $75 million.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetsCurrentAbstract', window );"><strong>Current assets:</strong></a></td>
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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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Short-term investments</a></td>
<td class="nump">1,877,943<span></span>
</td>
<td class="nump">1,805,252<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrent', window );">Contracts receivable</a></td>
<td class="nump">10,452<span></span>
</td>
<td class="nump">12,759<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryNet', window );">Inventories</a></td>
<td class="nump">11,057<span></span>
</td>
<td class="nump">8,582<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherAssetsCurrent', window );">Other current assets</a></td>
<td class="nump">98,686<span></span>
</td>
<td class="nump">102,473<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetsCurrent', window );">Total current assets</a></td>
<td class="nump">2,373,949<span></span>
</td>
<td class="nump">2,207,886<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="nump">133,519<span></span>
</td>
<td class="nump">132,160<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsNet', window );">Patents, net</a></td>
<td class="nump">25,220<span></span>
</td>
<td class="nump">24,032<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent', window );">Long-term deferred tax assets</a></td>
<td class="nump">277,247<span></span>
</td>
<td class="nump">290,796<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherAssetsNoncurrent', window );">Deposits and other assets</a></td>
<td class="nump">25,954<span></span>
</td>
<td class="nump">12,910<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets</a></td>
<td class="nump">2,835,889<span></span>
</td>
<td class="nump">2,667,784<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AccountsPayableCurrent', window );">Accounts payable</a></td>
<td class="nump">13,332<span></span>
</td>
<td class="nump">28,660<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeRelatedLiabilitiesCurrent', window );">Accrued compensation</a></td>
<td class="nump">16,264<span></span>
</td>
<td class="nump">29,268<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrent', window );">Accrued liabilities</a></td>
<td class="nump">45,130<span></span>
</td>
<td class="nump">47,503<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccruedIncomeTaxesCurrent', window );">Income taxes payable</a></td>
<td class="nump">18,401<span></span>
</td>
<td class="nump">858<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent', window );">Current portion of long-term obligations</a></td>
<td class="nump">14,500<span></span>
</td>
<td class="nump">13,749<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred contract revenue</a></td>
<td class="nump">144,846<span></span>
</td>
<td class="nump">160,256<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrent', window );">Total current liabilities</a></td>
<td class="nump">252,473<span></span>
</td>
<td class="nump">280,294<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityNoncurrent', window );">Long-term deferred contract revenue</a></td>
<td class="nump">542,416<span></span>
</td>
<td class="nump">567,359<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">1 percent convertible senior notes</a></td>
<td class="nump">577,415<span></span>
</td>
<td class="nump">568,215<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="top.Show.showAR( this, 'defref_ions_LongTermObligationsNoncurrent', window );">Long-term obligations, less current portion</a></td>
<td class="nump">16,305<span></span>
</td>
<td class="nump">4,914<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermLoansFromBank', window );">Long-term mortgage debt</a></td>
<td class="nump">59,860<span></span>
</td>
<td class="nump">59,842<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Liabilities', window );">Total liabilities</a></td>
<td class="nump">1,448,469<span></span>
</td>
<td class="nump">1,480,624<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_CommonStockValue', window );">Common stock, $0.001 par value; 300,000,000 shares authorized, 139,623,937 and 137,928,828 shares issued and outstanding at March 31, 2019 (unaudited) and December 31, 2018, respectively</a></td>
<td class="nump">140<span></span>
</td>
<td class="nump">138<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdditionalPaidInCapitalCommonStock', window );">Additional paid-in capital</a></td>
<td class="nump">2,117,969<span></span>
</td>
<td class="nump">2,047,250<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax', window );">Accumulated other comprehensive loss</a></td>
<td class="num">(27,608)<span></span>
</td>
<td class="num">(32,016)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RetainedEarningsAccumulatedDeficit', window );">Accumulated deficit</a></td>
<td class="num">(882,850)<span></span>
</td>
<td class="num">(967,293)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquity', window );">Total Ionis stockholders' equity</a></td>
<td class="nump">1,207,651<span></span>
</td>
<td class="nump">1,048,079<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterest', window );">Noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">179,769<span></span>
</td>
<td class="nump">139,081<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Total stockholders' equity</a></td>
<td class="nump">1,387,420<span></span>
</td>
<td class="nump">1,187,160<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquity', window );">Total liabilities and stockholders' equity</a></td>
<td class="nump">$ 2,835,889<span></span>
</td>
<td class="nump">$ 2,667,784<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LongTermObligationsNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt and lease obligation, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_LongTermObligationsNoncurrent</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(15)(b)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=6879938&amp;loc=d3e572229-122910<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(15)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=6876686&amp;loc=d3e534808-122878<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Accumulated change in equity from transactions and other events and circumstances from non-owner sources, net of tax effect, at period end. Excludes Net Income (Loss), and accumulated changes in equity from transactions resulting from investments by owners and distributions to owners. Includes foreign currency translation items, certain pension adjustments, unrealized gains and losses on certain investments in debt and equity securities, other than temporary impairment (OTTI) losses related to factors other than credit losses on available-for-sale and held-to-maturity debt securities that an entity does not intend to sell and it is not more likely than not that the entity will be required to sell before recovery of the amortized cost basis, as well as changes in the fair value of derivatives related to the effective portion of a designated cash flow hedge.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=d3e637-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14A<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669686-108580<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=d3e681-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all assets that are recognized. Assets are probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(11))<br> -URI http://asc.fasb.org/extlink&amp;oid=6876686&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(12))<br> -URI http://asc.fasb.org/extlink&amp;oid=6879938&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all assets that are expected to be realized in cash, sold, or consumed within one year (or the normal operating cycle, if longer). Assets are probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=82887183&amp;loc=d3e6801-107765<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.9)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=82887183&amp;loc=d3e6676-107765<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_AvailableForSaleSecuritiesDebtSecuritiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109979856&amp;loc=d3e26626-111562<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashAndCashEquivalentsAtCarryingValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3044-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=82887183&amp;loc=d3e6676-107765<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.1)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130531-203044<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130533-203044<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130532-203044<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130531-203044<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130549-203045<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130532-203044<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130531-203044<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleDebtNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConvertibleDebtNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after allocation of valuation allowances and deferred tax liability, of deferred tax asset attributable to deductible differences and carryforwards, with jurisdictional netting and classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=84176650&amp;loc=d3e31917-109318<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=84176650&amp;loc=d3e31931-109318<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32537-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent</td>
</tr>
<tr>
<td style="padding-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_EmployeeRelatedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeRelatedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FiniteLivedIntangibleAssetsNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after amortization of assets, excluding financial assets and goodwill, lacking physical substance with a finite life.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetsNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=82887183&amp;loc=d3e6676-107765<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 35<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=68049868&amp;loc=d3e3927-108312<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.6(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Liabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all liabilities that are recognized. Liabilities are probable future sacrifices of economic benefits arising from present obligations of an entity to transfer assets or provide services to other entities in the future.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19-26)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_Liabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesAndStockholdersEquity">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=6876686&amp;loc=d3e534808-122878<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(25))<br> -URI http://asc.fasb.org/extlink&amp;oid=6879938&amp;loc=d3e572229-122910<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(32))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.21)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_LongTermDebtAndCapitalLeaseObligationsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt and capital leases due within one year or the normal operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent</td>
</tr>
<tr>
<td style="padding-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_LongTermLoansFromBank">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of loans from a bank with maturities initially due after one year or beyond the operating cycle if longer, excluding current portion.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI http://asc.fasb.org/extlink&amp;oid=6876686&amp;loc=d3e534808-122878<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16)(a)(2))<br> -URI http://asc.fasb.org/extlink&amp;oid=6879938&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermLoansFromBank</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total of all stockholders' equity (deficit) items, net of receivables from officers, directors, owners, and affiliates of the entity which is directly or indirectly attributable to that ownership interest in subsidiary equity which is not attributable to the parent (that is, noncontrolling interest, previously referred to as minority interest).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(24))<br> -URI http://asc.fasb.org/extlink&amp;oid=6879938&amp;loc=d3e572229-122910<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.31)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=6876686&amp;loc=d3e534808-122878<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAssetsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of current assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.8)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of noncurrent assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.17)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherAssetsNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(14))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -URI http://asc.fasb.org/extlink&amp;oid=6879938&amp;loc=d3e572229-122910<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(13))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RetainedEarningsAccumulatedDeficit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cumulative amount of the reporting entity's undistributed earnings or deficit.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(3))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(4))<br> -URI http://asc.fasb.org/extlink&amp;oid=6879938&amp;loc=d3e572229-122910<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=27012166&amp;loc=d3e187085-122770<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RetainedEarningsAccumulatedDeficit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquity">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total of all stockholders' equity (deficit) items, net of receivables from officers, directors, owners, and affiliates of the entity which are attributable to the parent. The amount of the economic entity's stockholders' equity attributable to the parent excludes the amount of stockholders' equity which is allocable to that ownership interest in subsidiary equity which is not attributable to the parent (noncontrolling interest, minority interest). This excludes temporary equity and is sometimes called permanent equity.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 4.E)<br> -URI http://asc.fasb.org/extlink&amp;oid=27010918&amp;loc=d3e74512-122707<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(31))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td style="padding-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>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_StockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</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_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of stockholders' equity (deficit), net of receivables from officers, directors, owners, and affiliates of the entity, attributable to both the parent and noncontrolling interests. Amount excludes temporary equity. Alternate caption for the concept is permanent equity.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4568740-111683<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4I<br> -URI http://asc.fasb.org/extlink&amp;oid=84234705&amp;loc=SL4590271-111686<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4568447-111683<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6832101344">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited) (Parenthetical) - $ / shares<br></strong></div></th>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="nump">139,623,937<span></span>
</td>
<td class="nump">137,928,828<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CommonStockSharesOutstanding', window );">Common stock, shares outstanding (in shares)</a></td>
<td class="nump">139,623,937<span></span>
</td>
<td class="nump">137,928,828<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
<td><strong> Data Type:</strong></td>
<td>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesAuthorized</td>
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<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>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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<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_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td>instant</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_LiabilitiesAndStockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityAbstract</td>
</tr>
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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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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ConvertibleSeniorNotes1PercentMember</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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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6831992944">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited) - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 297,214<span></span>
</td>
<td class="nump">$ 144,419<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostOfGoodsAndServicesSold', window );">Cost of products sold</a></td>
<td class="nump">1,041<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ResearchDevelopmentAndPatentExpense', window );">Research, development and patent</a></td>
<td class="nump">106,417<span></span>
</td>
<td class="nump">104,067<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SellingGeneralAndAdministrativeExpense', window );">Selling, general and administrative</a></td>
<td class="nump">68,221<span></span>
</td>
<td class="nump">43,653<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">175,679<span></span>
</td>
<td class="nump">147,720<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="nump">121,535<span></span>
</td>
<td class="num">(3,301)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentIncomeNet', window );">Investment income</a></td>
<td class="nump">12,142<span></span>
</td>
<td class="nump">3,610<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InterestExpense', window );">Interest expense</a></td>
<td class="num">(11,599)<span></span>
</td>
<td class="num">(10,938)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherNonoperatingIncomeExpense', window );">Other expenses</a></td>
<td class="num">(147)<span></span>
</td>
<td class="num">(168)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments', window );">Income (loss) before income tax expense</a></td>
<td class="nump">121,931<span></span>
</td>
<td class="num">(10,797)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Income tax expense</a></td>
<td class="num">(31,047)<span></span>
</td>
<td class="num">(15)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net income (loss)</a></td>
<td class="nump">90,884<span></span>
</td>
<td class="num">(10,812)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAttributableToNoncontrollingInterest', window );">Net (income) loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="num">(6,441)<span></span>
</td>
<td class="nump">9,392<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="nump">$ 84,443<span></span>
</td>
<td class="num">$ (1,420)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="nump">$ 0.63<span></span>
</td>
<td class="num">$ (0.01)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Shares used in computing basic net income (loss) per share (in shares)</a></td>
<td class="nump">138,582<span></span>
</td>
<td class="nump">125,330<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net income (loss) per share (in dollars per share)</a></td>
<td class="nump">$ 0.62<span></span>
</td>
<td class="num">$ (0.01)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net income (loss) per share (in shares)</a></td>
<td class="nump">141,537<span></span>
</td>
<td class="nump">125,330<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 68,088<span></span>
</td>
<td class="nump">$ 42,023<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">59,711<span></span>
</td>
<td class="nump">41,081<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=us-gaap_ProductMember', window );">TEGSEDI Product Sales, Net [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="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">6,754<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="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">1,623<span></span>
</td>
<td class="nump">942<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">Research and Development Revenue Under Collaborative Agreements [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="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 229,126<span></span>
</td>
<td class="nump">$ 102,396<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ResearchDevelopmentAndPatentExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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<tr>
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<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_CostOfGoodsAndServicesSold">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.2(a),(d))<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td><strong> Data Type:</strong></td>
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<tr>
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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_CostsAndExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
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<tr>
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</tr>
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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</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_EarningsPerShareBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873790&amp;loc=SL114874131-224263<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1337-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI http://asc.fasb.org/extlink&amp;oid=109256448&amp;loc=d3e4984-109258<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(21))<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1252-109256<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873765&amp;loc=SL114874048-224260<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=SL5780133-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI http://asc.fasb.org/extlink&amp;oid=109256448&amp;loc=d3e4984-109258<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1252-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873765&amp;loc=SL114874048-224260<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1337-109256<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(21))<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=SL5780133-109256<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873790&amp;loc=SL114874131-224263<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations before deduction of income tax expense (benefit) and income (loss) attributable to noncontrolling interest, and addition of income (loss) from equity method investments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08.(h)(1)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=26873400&amp;loc=d3e23780-122690<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments</td>
</tr>
<tr>
<td style="padding-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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=26873400&amp;loc=d3e23780-122690<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109238882&amp;loc=d3e38679-109324<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of the cost of borrowed funds accounted for as interest expense.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6450988&amp;loc=d3e26243-108391<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=114775744&amp;loc=d3e28555-108399<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (210.5-03(11))<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04.9)<br> -URI http://asc.fasb.org/extlink&amp;oid=114873765&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.9)<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.7(a),(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.8)<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669619-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873765&amp;loc=SL114874048-224260<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669625-108580<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(18))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873790&amp;loc=SL114874131-224263<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of Net Income (Loss) attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669625-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669619-108580<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4J<br> -URI http://asc.fasb.org/extlink&amp;oid=84234705&amp;loc=SL4591551-111686<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-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_NonoperatingIncomeExpenseAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NonoperatingIncomeExpenseAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The net result for the period of deducting operating expenses from operating revenues.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.9)<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherNonoperatingIncomeExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669619-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669625-108580<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4J<br> -URI http://asc.fasb.org/extlink&amp;oid=84234705&amp;loc=SL4591551-111686<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3000-108585<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8933-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=84234705&amp;loc=SL4591552-111686<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130543-203045<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130539-203045<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130545-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 30<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=68048583&amp;loc=d3e3636-108311<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1505-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1448-109256<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
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<tr>
<td><strong> Name:</strong></td>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6812050880">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) (Unaudited) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract', window );"><strong>CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net income (loss)</a></td>
<td class="nump">$ 90,884<span></span>
</td>
<td class="num">$ (10,812)<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="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax', window );">Unrealized gains (losses) on debt securities, net of tax</a></td>
<td class="nump">4,324<span></span>
</td>
<td class="num">(1,530)<span></span>
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<td class="nump">84<span></span>
</td>
<td class="nump">55<span></span>
</td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest', window );">Comprehensive income (loss)</a></td>
<td class="nump">95,292<span></span>
</td>
<td class="num">(12,287)<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="top.Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest', window );">Comprehensive (income) loss attributable to noncontrolling interests</a></td>
<td class="nump">6,442<span></span>
</td>
<td class="num">(9,399)<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTax', window );">Comprehensive income (loss) attributable to Ionis Pharmaceuticals, Inc. stockholders</a></td>
<td class="nump">$ 88,850<span></span>
</td>
<td class="num">$ (2,888)<span></span>
</td>
</tr>
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<div style="display: none;">
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=d3e557-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669625-108580<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669619-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.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 (loss) and other comprehensive income (loss), attributable to noncontrolling interests. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669625-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=84234705&amp;loc=SL4591552-111686<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669619-108580<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 21<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4613674-111683<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569643-111683<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest</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> Period Type:</strong></td>
<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_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=84234705&amp;loc=SL4591552-111686<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669619-108580<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669625-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
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</table></div>
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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6450520&amp;loc=d3e32583-110901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=109240241&amp;loc=d3e32157-110900<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=109240241&amp;loc=d3e32211-110900<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=109240241&amp;loc=d3e32022-110900<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (a-c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669646-108580<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td>xbrli:monetaryItemType</td>
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<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after tax, before reclassification adjustments, of unrealized holding gain (loss) on available-for-sale securities.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669646-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax</td>
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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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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669619-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669625-108580<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4J<br> -URI http://asc.fasb.org/extlink&amp;oid=84234705&amp;loc=SL4591551-111686<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3000-108585<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8933-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=84234705&amp;loc=SL4591552-111686<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6834565904">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY (Unaudited) - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th"><div>Common Stock [Member]</div></th>
<th class="th"><div>Additional Paid In Capital [Member]</div></th>
<th class="th"><div>Accumulated Other Comprehensive Loss [Member]</div></th>
<th class="th"><div>Accumulated Deficit [Member]</div></th>
<th class="th"><div>Total Ionis Stockholders' Equity [Member]</div></th>
<th class="th"><div>Noncontrolling Interest in Akcea Therapeutics, Inc. [Member]</div></th>
<th class="th"><div>Total</div></th>
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<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2017</a></td>
<td class="nump">$ 125<span></span>
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<td class="nump">$ 1,553,681<span></span>
</td>
<td class="num">$ (31,759)<span></span>
</td>
<td class="num">$ (1,241,034)<span></span>
</td>
<td class="nump">$ 281,013<span></span>
</td>
<td class="nump">$ 84,267<span></span>
</td>
<td class="nump">$ 365,280<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2017</a></td>
<td class="nump">124,976<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#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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</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<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="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (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">(1,420)<span></span>
</td>
<td class="num">(1,420)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,420)<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="top.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">(1,530)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,530)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,530)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">55<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">55<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">55<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="top.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">5,664<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">5,664<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">5,664<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="top.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">473<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">28,451<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">28,451<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">28,451<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestPeriodIncreaseDecrease', window );">Noncontrolling interest in Akcea Therapetuics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,842)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,842)<span></span>
</td>
<td class="nump">1,443<span></span>
</td>
<td class="num">(9,399)<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Mar. 31, 2018</a></td>
<td class="nump">$ 125<span></span>
</td>
<td class="nump">1,576,954<span></span>
</td>
<td class="num">(33,234)<span></span>
</td>
<td class="num">(1,242,454)<span></span>
</td>
<td class="nump">301,391<span></span>
</td>
<td class="nump">85,710<span></span>
</td>
<td class="nump">387,101<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Mar. 31, 2018</a></td>
<td class="nump">125,449<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2018</a></td>
<td class="nump">$ 138<span></span>
</td>
<td class="nump">2,047,250<span></span>
</td>
<td class="num">(32,016)<span></span>
</td>
<td class="num">(967,293)<span></span>
</td>
<td class="nump">1,048,079<span></span>
</td>
<td class="nump">139,081<span></span>
</td>
<td class="nump">1,187,160<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2018</a></td>
<td class="nump">137,929<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.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>
<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="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (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="nump">84,443<span></span>
</td>
<td class="nump">84,443<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">84,443<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">4,324<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">4,324<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">4,324<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">84<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">84<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">84<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">67,057<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">67,059<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">67,059<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">1,825<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">45,505<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">45,505<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">45,505<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of share-based awards</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(7,597)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(7,597)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(7,597)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of share-based awards (in shares)</a></td>
<td class="num">(130)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestPeriodIncreaseDecrease', window );">Noncontrolling interest in Akcea Therapetuics, Inc.</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(34,246)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(34,246)<span></span>
</td>
<td class="nump">40,688<span></span>
</td>
<td class="nump">6,442<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Mar. 31, 2019</a></td>
<td class="nump">$ 140<span></span>
</td>
<td class="nump">$ 2,117,969<span></span>
</td>
<td class="num">$ (27,608)<span></span>
</td>
<td class="num">$ (882,850)<span></span>
</td>
<td class="nump">$ 1,207,651<span></span>
</td>
<td class="nump">$ 179,769<span></span>
</td>
<td class="nump">$ 1,387,420<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Mar. 31, 2019</a></td>
<td class="nump">139,624<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of adjustment to stockholders' equity associated with an employee's income tax withholding obligation as part of a net-share settlement of a share-based award.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of increase to additional paid-in capital (APIC) from recognition of equity-based compensation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=109196918&amp;loc=d3e11149-113907<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5047-113901<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 13<br> -URI http://asc.fasb.org/extlink&amp;oid=109196918&amp;loc=d3e11178-113907<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 35<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=79507207&amp;loc=d3e4534-113899<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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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>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInStockholdersEquityRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestPeriodIncreaseDecrease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Net Increase or Decrease in balance of noncontrolling interest in the subsidiary during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4568740-111683<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestPeriodIncreaseDecrease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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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_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669619-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873765&amp;loc=SL114874048-224260<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669625-108580<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(18))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873790&amp;loc=SL114874131-224263<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after tax and reclassification adjustments, of appreciation (loss) in value of unsold available-for-sale securities, attributable to parent entity. Excludes amounts related to other than temporary impairment (OTTI) loss.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569643-111683<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6450520&amp;loc=d3e32583-110901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=109240241&amp;loc=d3e32157-110900<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=109240241&amp;loc=d3e32211-110900<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=109240241&amp;loc=d3e32022-110900<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (a-c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669646-108580<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>For net-share settlement of share-based awards when the employer settles employees' income tax withholding obligations, this element represents the number of shares the employees use to repay the employer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares (or other type of equity) issued during the period as a result of any equity-based compensation plan other than an employee stock ownership plan (ESOP), net of any shares forfeited. Shares issued could result from the issuance of restricted stock, the exercise of stock options, stock issued under employee stock purchase plans, and/or other employee benefit plans.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=27012166&amp;loc=d3e187085-122770<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Gross value of stock (or other type of equity) issued during the period as a result of any equity-based compensation plan other than an employee stock ownership plan (ESOP). Stock issued could result from the issuance of restricted stock, the exercise of stock options, stock issued under employee stock purchase plans, and/or other employee benefit plans.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of stockholders' equity (deficit), net of receivables from officers, directors, owners, and affiliates of the entity, attributable to both the parent and noncontrolling interests. Amount excludes temporary equity. Alternate caption for the concept is permanent equity.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4568740-111683<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4I<br> -URI http://asc.fasb.org/extlink&amp;oid=84234705&amp;loc=SL4590271-111686<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4568447-111683<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6833868208">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Unaudited) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Operating activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net income (loss)</a></td>
<td class="nump">$ 90,884<span></span>
</td>
<td class="num">$ (10,812)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Adjustments to reconcile net loss to net cash provided by operating activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Depreciation', window );">Depreciation</a></td>
<td class="nump">3,073<span></span>
</td>
<td class="nump">2,363<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AmortizationOfIntangibleAssets', window );">Amortization of patents</a></td>
<td class="nump">470<span></span>
</td>
<td class="nump">443<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments', window );">Amortization of premium on investments, net</a></td>
<td class="num">(2,433)<span></span>
</td>
<td class="nump">1,192<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="nump">474<span></span>
</td>
<td class="nump">441<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AmortizationOfDebtDiscountPremium', window );">Amortization of convertible senior notes discount</a></td>
<td class="nump">8,726<span></span>
</td>
<td class="nump">8,083<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensation', window );">Stock-based compensation expense</a></td>
<td class="nump">45,505<span></span>
</td>
<td class="nump">28,451<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetImpairmentCharges', window );">Non-cash losses related to patents, licensing and property, plant and equipment</a></td>
<td class="nump">14<span></span>
</td>
<td class="nump">175<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredIncomeTaxExpenseBenefit', window );">Provision for deferred income taxes</a></td>
<td class="nump">13,549<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOperatingCapitalAbstract', window );"><strong>Changes in operating assets and liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerAsset', window );">Contracts receivable</a></td>
<td class="nump">4,908<span></span>
</td>
<td class="nump">26,097<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInInventories', window );">Inventories</a></td>
<td class="num">(2,475)<span></span>
</td>
<td class="nump">922<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherOperatingAssets', window );">Other current and long-term assets</a></td>
<td class="nump">1,802<span></span>
</td>
<td class="nump">11,422<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInAccountsPayable', window );">Accounts payable</a></td>
<td class="num">(17,191)<span></span>
</td>
<td class="num">(13,144)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities', window );">Accrued compensation</a></td>
<td class="num">(13,004)<span></span>
</td>
<td class="num">(12,985)<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="top.Show.showAR( this, 'defref_ions_IncreaseDecreaseInAccruedAndDeferredLiabilities', window );">Accrued liabilities and deferred rent</a></td>
<td class="nump">13,756<span></span>
</td>
<td class="num">(1,695)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="num">(40,353)<span></span>
</td>
<td class="num">(27,788)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInOperatingActivities', window );">Net cash provided by operating activities</a></td>
<td class="nump">107,705<span></span>
</td>
<td class="nump">13,165<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract', window );"><strong>Investing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt', window );">Purchases of short-term investments</a></td>
<td class="num">(492,781)<span></span>
</td>
<td class="num">(91,157)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities', window );">Proceeds from the sale of short-term investments</a></td>
<td class="nump">426,868<span></span>
</td>
<td class="nump">173,724<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment', window );">Purchases of property, plant and equipment</a></td>
<td class="num">(3,229)<span></span>
</td>
<td class="num">(2,343)<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="top.Show.showAR( this, 'defref_ions_PaymentsToAcquireLicensesAndOtherAssets', window );">Acquisition of licenses and other assets, net</a></td>
<td class="num">(1,032)<span></span>
</td>
<td class="num">(738)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInInvestingActivities', window );">Net cash provided by (used in) investing activities</a></td>
<td class="num">(70,174)<span></span>
</td>
<td class="nump">79,486<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract', window );"><strong>Financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Proceeds from equity awards</a></td>
<td class="nump">67,057<span></span>
</td>
<td class="nump">5,675<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards</a></td>
<td class="num">(7,597)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsOfStockIssuanceCosts', window );">Offering costs paid</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(451)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivities', window );">Net cash provided by financing activities</a></td>
<td class="nump">59,460<span></span>
</td>
<td class="nump">5,224<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect', window );">Net increase in cash and cash equivalents</a></td>
<td class="nump">96,991<span></span>
</td>
<td class="nump">97,875<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at beginning of period</a></td>
<td class="nump">278,820<span></span>
</td>
<td class="nump">129,630<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at end of period</a></td>
<td class="nump">375,811<span></span>
</td>
<td class="nump">227,505<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SupplementalCashFlowInformationAbstract', window );"><strong>Supplemental disclosures of cash flow information:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InterestPaidNet', window );">Interest paid</a></td>
<td class="nump">667<span></span>
</td>
<td class="nump">644<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract', window );"><strong>Supplemental disclosures of non-cash investing and financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability', window );">Right-of-use assets obtained in exchange for lease obligations</a></td>
<td class="nump">13,557<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NonCashCapitalAndPatentExpenditures', window );">Amounts accrued for capital and patent expenditures</a></td>
<td class="nump">$ 1,864<span></span>
</td>
<td class="nump">$ 2,091<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_IncreaseDecreaseInAccruedAndDeferredLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the aggregate amount of expenses incurred but not yet paid and deferred liabilities due within one year or operating cycle.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_IncreaseDecreaseInAccruedAndDeferredLiabilities</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_PaymentsToAcquireLicensesAndOtherAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for acquisition of licenses and other assets not otherwise defined in the taxonomy.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_PaymentsToAcquireLicensesAndOtherAssets</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_AmortizationOfDebtDiscountPremium">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of noncash expense included in interest expense to amortize debt discount and premium associated with the related debt instruments. Excludes amortization of financing costs. Alternate captions include noncash interest expense.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=114775744&amp;loc=d3e28541-108399<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.8)<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfDebtDiscountPremium</td>
</tr>
<tr>
<td style="padding-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_AmortizationOfFinancingCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense attributable to debt issuance costs.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=114775744&amp;loc=d3e28555-108399<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=6388964&amp;loc=d3e16225-109274<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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</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_AssetImpairmentCharges">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of write-down of assets recognized in the income statement. Includes, but is not limited to, losses from tangible assets, intangible assets and goodwill.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=109226348&amp;loc=d3e2420-110228<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetImpairmentCharges</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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3521-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3044-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=98513485&amp;loc=SL98516268-108586<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in cash and cash equivalents, and cash and cash equivalents restricted to withdrawal or usage; excluding 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 230<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=98513438&amp;loc=d3e33268-110906<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect</td>
</tr>
<tr>
<td style="padding-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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredIncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred income tax expense (benefit) pertaining to income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI http://asc.fasb.org/extlink&amp;oid=34349781&amp;loc=d3e330036-122817<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=26873400&amp;loc=d3e23780-122690<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32639-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredIncomeTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-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_Depreciation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_IncreaseDecreaseInAccountsPayable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_IncreaseDecreaseInContractWithCustomerAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
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<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_IncreaseDecreaseInOtherEmployeeRelatedLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOtherOperatingAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InterestPaidNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=98513485&amp;loc=d3e4297-108586<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 17<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3367-108585<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3536-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InterestPaidNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInFinancingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInFinancingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInInvestingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInInvestingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInOperatingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3536-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3521-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInOperatingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsOfStockIssuanceCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for cost incurred directly with the issuance of an equity security.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsOfStockIssuanceCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to satisfy an employee's income tax withholding obligation as part of a net-share settlement of a share-based award.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3291-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 25<br> -Paragraph 19A<br> -URI http://asc.fasb.org/extlink&amp;oid=107668666&amp;loc=SL79513924-113897<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3213-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3151-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109979856&amp;loc=d3e26853-111562<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<a href="javascript:void(0);" onclick="top.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>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from issuance of shares under share-based compensation arrangement. Issuance includes, but is not limited to, exercise of stock options and similar instruments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=SL79508275-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3255-108585<br></p></div>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3151-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3179-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109979856&amp;loc=d3e26853-111562<br></p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669619-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669625-108580<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4J<br> -URI http://asc.fasb.org/extlink&amp;oid=84234705&amp;loc=SL4591551-111686<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3000-108585<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8933-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=84234705&amp;loc=SL4591552-111686<br></p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of increase in right-of-use asset obtained in exchange for operating lease liability.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI http://asc.fasb.org/extlink&amp;oid=77888399&amp;loc=SL77918982-209971<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918686-209980<br></p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The aggregate amount of noncash, equity-based employee remuneration. This may include the value of stock or unit options, amortization of restricted stock or units, and adjustment for officers' compensation. As noncash, this element is an add back when calculating net cash generated by operating activities using the indirect method.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br></p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6825007360">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basis of Presentation<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2019</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Basis of Presentation [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="top.Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock', window );">Basis of Presentation</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.&#160; Basis of Presentation</div><div><br /></div><div style="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 months ended March 31, 2019 and 2018 on the same basis as the audited financial statements for the year ended December 31, 2018. 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. Results for the interim periods are not necessarily indicative of the results 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, 2018 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals,&#160;Inc. and the consolidated results of our majority owned affiliate,&#160;Akcea Therapeutics, Inc. and its wholly owned subsidiaries. We formed Akcea in December 2014. </font>In July 2017, Akcea completed an <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">initial public offering, or IPO,</font> and therefore, beginning in July 2017, we no longer owned 100 percent of Akcea. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub>, increasing our ownership to approximately 76 percent at March 31, 2019. We reflected the increase in our ownership in these financial statements. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Refer to the section titled &#8220;Noncontrolling Interest in Akcea&#8221; in Note 2, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies,</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for further information related to our accounting for our investment in Akcea.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unless the context requires otherwise, &#8220;Ionis&#8221;, &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221; refers to Ionis Pharmaceuticals, Inc. and its majority owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries.</div><div><br /></div></div><span></span>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for organization, consolidation and basis of presentation of financial statements disclosure.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 205<br> -URI http://asc.fasb.org/topic&amp;trid=2122149<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -URI http://asc.fasb.org/topic&amp;trid=2197479<br></p></div>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6816070512">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2019</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccountingPoliciesAbstract', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SignificantAccountingPoliciesTextBlock', window );">Significant Accounting Policies</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2.&#160; Significant Accounting Policies</div><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><font style="background-color: #FFFFFF;">Revenue Recognition</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Our Revenue Sources</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts in deferred revenue on our consolidated balance sheet.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Commercial Revenue: TEGSEDI Product Sales, net</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018. </font>In the U.S., TEGSEDI is distributed through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients. In Germany, TEGSEDI is distributed through a non-exclusive distribution model with a 3PL that takes title to TEGSEDI. The 3PL is our sole customer in Germany. The 3PL in Germany then distributes TEGSEDI to hospitals and pharmacies.</font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Research and development revenue under collaborative agreements</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We often 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.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We provide details about our collaboration agreements in Note 7, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements,</font> in our Annual Report on Form 10-K for the year ended December 31, 2018<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">.</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</font>Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Steps to Recognize Revenue</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:</font></div><div><br /></div><div><br /></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">1.</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Identify the contract</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</font></div><div><br /></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We and our partner approved the contract and we are both committed to perform our obligations;</font></div></td></tr></table></div></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have identified our rights, our partner&#8217;s rights and the payment terms;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and</font></div></td></tr></table></div></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We believe collectability is probable.</font></div></td></tr></table></div></div><div style="margin-bottom: 10pt;"><br /></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">2.</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Identify the performance obligations</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We next identify the distinct goods and services we are required to provide under the contract. Accounting rules refer to these as our performance obligations. We typically have only one performance obligation at the inception of a contract, which is to perform R&amp;D services.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Often times we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights. These items are contingent upon future events that may not occur. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">3.</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Determine the transaction price</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and are usually based on scientific progress. For example, in the first quarter of 2019, we earned $35 million in milestone payments from Roche when it dosed the first patient in the Phase 3 study of IONIS-HTT<sub>Rx </sub>(RG6042) <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">because we do not have any performance obligations related to these milestone payments as Roche is conducting the Phase 3 study of IONIS-HTT</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</font> At December 31, 2018, we determined it was not probable that we could earn these milestone payments.&#160;As such, we did not recognize any revenue associated with the milestone payments in 2018.</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">4.</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Allocate the transaction price</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Estimated future product sales;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Estimated royalties on future product sales;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Contractual milestone payments;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Expenses we expect to incur;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Income taxes; and</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">A discount rate.</font></div></td></tr></table></div></div><div><br /></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The number of internal hours we estimate we will spend performing these services;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The estimated cost of work we will perform;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The estimated cost of work that we will contract with third parties to perform; and</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The estimated cost of API we will use.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">5.</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Recognize revenue</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</font></font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize royalty revenue in the period in which the counterparty sells the related product, which in certain cases may require us to estimate our royalty revenue. </font>We recognize royalties from SPINRAZA sales in the period Biogen records the sale of SPINRAZA.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Commercial Revenue: TEGSEDI Product Sales, net</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize TEGSEDI product sales in the period </font>when our customer obtains control of TEGSEDI, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative expenses in our condensed consolidated statements of operations. Otherwise payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues, taxes collected from customers relating to product sales and remitted to governmental authorities.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Reserves for TEGSEDI Product Sales</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We record TEGSEDI product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates, co-pay assistance and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as reductions of accounts receivable when the amount is payable to our customer or a current liability when the amount is payable to a party other than our customer in our condensed consolidated balance sheet. In certain cases, our estimates include a range of possible outcomes that are probability-weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net TEGSEDI product sales in the respective period.</font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following are the components of variable consideration related to TEGSEDI product sales:</font></div><div><br /></div><div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Chargebacks: </font>In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We record reserves for these chargebacks related to TEGSEDI product sales to our U.S. customer during the reporting period. We also estimate the amount of product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods.</font></div><div><br /></div><div><br /></div><div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Government rebates</font>: We are subject to discount obligations under government programs, including Medicaid programs and Medicare in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability-weighted for the estimated payer mix. We record these reserves as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments.</font></div><div><br /></div><div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Trade discounts and allowances: </font>We provide customary invoice discounts on TEGSEDI product sales to our U.S. customer for prompt payment. We record this discount as a reduction of TEGSEDI product sales in the period in which we recognize the related product revenue. In addition, we receive and pay for various distribution services from our U.S. customer and wholesalers in our U.S. distribution channel. For services we receive that are either not distinct from the sale of TEGSEDI or for which we cannot reasonably estimate the fair value, we classify such fees as a reduction of TEGSEDI product sales.</font></div><div><br /></div><div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Product Returns: </font>Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the TEGSEDI&#8217;s expiration date. We estimate the amount of TEGSEDI product sales that our customer may return. We record our return estimate as an accrued refund liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales, in the same period we recognize the related sale. Based on our distribution model for TEGSEDI, contractual inventory limits with our customer and wholesalers and the price of TEGSEDI, we believe we will have minimal returns. Our customer in Germany only takes title to the product once it receives an order from a hospital or pharmacy and therefore does not maintain any inventory of TEGSEDI, as such we do not estimate returns in Germany.</font></div><div><br /></div><div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Other incentives: </font>In the U.S., we estimate reserves for other incentives including co-payment assistance we provide to patients with commercial insurance who have coverage and reside in states that allow co-payment assistance. We record a reserve for the amount we estimate we will pay for co-payment assistance. We base our reserve on the number of estimated claims and our estimate of the cost per claim related to TEGSEDI product sales that we have recognized as revenue. We record our other incentive reserve estimates as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales, in the same period we recognize the related sale.</font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Research and development revenue under collaboration agreements:</u></font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Upfront Payments</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we enter into a collaboration agreement with an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. For example, under our <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">collaboration agreement with Roche to</font><font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;for the treatment of complement-mediated diseases</font>, we received a $75 million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $75 million upfront payment using an input method over the estimated period of time we are providing R&amp;D services.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Milestone Payments</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because there is considerable uncertainty in the research and development processes that trigger these payments under our collaboration agreements. 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 we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the third quarter of 2017, we initiated a Phase 1/2a clinical study of IONIS-MAPT<sub>Rx </sub>in patients with mild Alzheimer&#8217;s disease. We earned a $10 million milestone payment from Biogen related to the initiation of this study. We added this payment to the transaction price and allocated it to our R&amp;D services performance obligation. We are recognizing revenue from this milestone payment over our estimated period of performance.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the first quarter of 2019, we recognized $35 million in milestone payments <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">when Roche dosed the first patient in a Phase 3 study for IONIS-HTT</font><sub>Rx</sub>. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We concluded that the milestone payments were not related to our R&amp;D services performance obligation. Therefore, we recognized these milestone payments in full in the first quarter of 2019.</font></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>License Fees</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generally recognize as revenue the total amount we determine to be the stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. </font>For example, in the first quarter of 2019, we earned a $150 million license fee when Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub> from us.</font></div><div><br /></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Amendments to Agreements</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If the goods and/or services are at a stand-alone selling price.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and at their stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the prevention of thrombosis. As part of the agreement, Bayer paid us a $100 million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and to initiate development of IONIS-FXI-L</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $75 million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and IONIS-FXI-L</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the 2017 amendment, we concluded we had a new agreement with three performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, to provide R&amp;D services and to deliver API. We allocated the $75 million transaction price to these performance obligations. </font>Refer to <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 7, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</font>, for further discussion <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">of our accounting treatment for our Bayer collaboration.</font></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Multiple Agreements</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Whether the agreements were negotiated together with a single objective;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Whether the goods and/or services promised under the agreements are a single performance obligation.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis.</font></font></div><div><br /></div><div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contract receivable to be unconditional. We typically receive payment within one quarter of billing our partner or customer</font>.</font></div><div><br /></div><div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled SPINRAZA Royalties</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen for SPINRAZA royalties. We include these unbilled amounts in other current assets on our condensed consolidated balance sheet.</font></div><div><br /></div><div><br /></div><div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Products Sold</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our cost of products sold includes manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of TEGSEDI. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of products sold. Prior to obtaining regulatory approval in July 2018, we expensed a significant portion of the costs we incurred to produce the TEGSEDI supply we are using in the commercial launch as research and development expense. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We previously recognized $0.3 million of costs to produce TEGSEDI related to the TEGSEDI commercial revenue we recognized in the</font> three months ended March 31, 2019.</font></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;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Prior to Akcea&#8217;s IPO in July 2017, we owned 100 percent of Akcea. From the closing of Akcea&#8217;s IPO in July 2017 through mid-April 2018, we owned approximately 68 percent<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font>of Akcea. In the second, third and fourth quarters of 2018, we received additional shares of Akcea&#8217;s stock related to our license of TEGSEDI and AKCEA-TTR-L<sub>Rx</sub> to Akcea, increasing our ownership percentage to approximately 75 percent. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub>, increasing our ownership to approximately 76 percent at March 31, 2019. We reflected this increase in our ownership percentage in these financial statements as an adjustment to noncontrolling interest. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The shares third parties own represent an interest in Akcea&#8217;s equity that is not controlled by us. However, as we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our condensed consolidated financial statements. We reflect the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock in a separate line on the statement of operations and a separate line within stockholders&#8217; equity in our condensed consolidated balance sheet. In addition, we record a noncontrolling interest adjustment to account for the stock options Akcea grants, which if exercised, will dilute our ownership in Akcea. This adjustment is a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized.</font></font></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;">Cash, cash equivalents and investments</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments. We use the specific identification method to determine the cost of securities sold.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At March 31, 2019, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in four privately-held companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd.</font></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;">Inventory valuation</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or market value under the first-in, first-out method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials they have alternative future uses. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency.</font></div><div style="text-align: justify;"><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We obtained the first regulatory approval for TEGSEDI in July 2018. At March 31, 2019 and December 31, 2018, our physical inventory for TEGSEDI included API that we produced prior to when we obtained regulatory approval and accordingly has no cost basis as we had previously expensed the costs as R&amp;D expenses.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We did not record any inventory write-offs for the three months ended March 31, 2019 and 2018. Total inventory was $11.1 million and $8.6 million as of </font>March 31, 2019 and December 31, 2018<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively.</font></font></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;">Leases</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Topic 842 Adoption</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In February 2016, the FASB issued amended accounting guidance related to lease accounting. This guidance supersedes the lease requirements we previously followed in Accounting Standards Codification, or ASC, Topic 840, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</font>, or Topic 840, and created a new lease accounting standard, Topic 842, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</font>, or Topic 842. Under Topic 842, an entity will record on its balance sheet all leases with a term longer than one year. Further, an entity will record a liability with a value equal to the present value of payments it will make over the life of the lease (lease liability) and an asset representing the underlying leased asset (right-of-use asset). The new accounting guidance requires entities to determine if its leases are operating or financing leases. Entities will recognize expense for operating leases on a straight-line basis as an operating expense. If an entity determines a lease is a financing&#160;lease, it will record</font></div><div><br /></div><div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. We adopted Topic 842 on January 1, 2019 and adjusted our opening balance sheet on that date for our right-of-use operating lease assets and operating lease liabilities. At adoption, we recorded $13.5 million in right-of-use operating lease assets and $18.5 million in operating lease liabilities, of which we classified $2 million as a current liability. We adopted Topic 842 using the available practical expedients<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> permitted under the transition guidance within the new standard, which among other things, allowed us to carry forward the historical lease classification of those leases we had in place as of January 1, 2019. </font>The adoption did not have an impact on our condensed consolidated statement of operations.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed consolidated balance sheet for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we will pay over the lease term.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</font>We determined the lease term at the commencement date of the lease, and in certain cases our lease term could include renewal options if we concluded we were reasonably certain that we will exercise the renewal option.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">As our current leases do not provide an interest rate implicit in the lease, we used our or Akcea&#8217;s incremental borrowing rate, based on the information available on the date we adopted Topic 842 in determining the present value of future payments. Our right-of-use operating lease asset also includes any lease payments we made and excludes any tenant improvement allowances we received. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</font></div><div><br /></div><div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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 and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our condensed consolidated balance sheet and we expense them as the services are provided.</div><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the United States Patent and Trademark Office, or foreign equivalent, issues the patent. We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. We evaluate patents and patent applications that we are not actively pursuing and write off any associated costs.</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;">Income Taxes</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act of 2017, or the Tax Act. The Tax Act created a new requirement on global intangible low-taxed income, or GILTI, earned by foreign subsidiaries for tax years beginning on or after January 1, 2018. The GILTI provisions require foreign subsidiary earnings in excess of an allowable return on the foreign subsidiary&#8217;s assets to be included in our U.S. income tax return. Under U.S. GAAP, we are permitted to make an accounting policy election to either treat taxes due on future inclusions in U.S. taxable income related to GILTI as a current-period expense when incurred or to factor such amounts into our measurement of deferred taxes. We have made the election to account for GILTI as a component of current taxes incurred rather than as a component of deferred taxes.</font></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;">Long-lived assets</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We evaluate long-lived assets, which include property, plant and equipment, right-of-use operating lease assets and patent costs acquired from third parties, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.</font></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;">Use of estimates</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The preparation of condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States requires us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. 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To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s loss per share by the weighted average shares we owned in Akcea during the period. 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Common stock from the following would have had an anti-dilutive effect on net loss per share:</font></div><div><br /></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1 percent convertible senior notes;</font></div></td></tr></table></div></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Dilutive stock options;</font></div></td></tr></table></div></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Unvested restricted stock units; and</font></div></td></tr></table></div></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Employee Stock Purchase Plan, or ESPP.</font></div></td></tr></table></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;">Convertible debt</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for convertible debt instruments that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate. We determine the carrying amount of the liability component by measuring the fair value of similar debt instruments that do not have the conversion feature. If no similar debt instrument exists, we estimate fair value by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities. To determine the fair value of the debt component we are required to use accounting estimates and assumptions. These estimates and assumptions are judgmental in nature and could have a significant impact on the determination of the debt component, and the associated non-cash interest expense.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method.</font></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;">Segment information</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have two operating segments, our Ionis Core segment and Akcea Therapeutics, our majority-owned affiliate. Akcea is </font>a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We provide segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviews to assess operating performance and to make operating decisions. We allocate a portion of Ionis&#8217; development, R&amp;D support and general and administrative expenses to Akcea for work Ionis performs on behalf of Akcea.</font></font></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;">Stock-based compensation expense</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, restricted stock units, or RSUs, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. 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We will adjust total unrecognized compensation cost for future forfeitures. We expect to recognize the cost of non-cash stock-based compensation expense related to non-vested stock options and RSUs over a weighted average amortization period of 1.4 years and 2.0 years, respectively.</div><div><br /></div><div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impact of recently issued accounting standards</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. The new standard is effective for annual and interim periods beginning after December 15, 2019. Early adoption is permitted for periods beginning after December 15, 2018. When we adopt the new standard, we will make any adjustments to beginning balances through a cumulative-effect adjustment to accumulated deficit on that date. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it will have on our condensed consolidated financial statements and disclosures.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. The updated guidance is effective for fiscal years beginning after December 31, 2019, and interim periods within those fiscal years. Early adoption is permitted in any interim period. We are currently assessing the effects this updated guidance could have on our condensed consolidated financial statements and timing of adoption.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2018, the FASB updated its disclosure requirements related to Level 1, 2 and 3 fair value measurements. The update included deletion and modification of certain disclosure requirements and additional disclosure related to Level 3 measurements. The guidance is effective for fiscal years beginning after December 31, 2019 and early adoption is permitted. We adopted this updated guidance on January 1, 2019 and it did not have a significant impact on our disclosures.</font></div><div><br /></div><div style="text-align: left;"><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). 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The &#8220;unit of account&#8221; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 72pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">We will use the &#8220;unit of account&#8221; concept when we receive consideration under a collaboration to determine when we recognize revenue or a contra expense</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 72pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we will not recognize revenue for the transaction</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The updated guidance is effective for public entities for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. 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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6825036896">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments<br></strong></div></th>
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<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 0.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3.&#160; Investments</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">As of March 31, 2019, we had invested our excess cash primarily in debt instruments of the U.S. Treasury, financial institutions, corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#8217;s, Standard &amp; Poor&#8217;s, or S&amp;P, or Fitch, respectively. We have established guidelines relative to diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.</font></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 the contract maturity of the available-for-sale securities we held as of March 31, 2019:</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><tr><td style="width: 83.04%; vertical-align: bottom; background-color: rgb(204, 238, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">One year or less</font></div></td><td style="width: 16.96%; vertical-align: bottom; background-color: rgb(204, 238, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">74%</font></div></td></tr><tr><td style="width: 83.04%; vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">After one year but within two years</font></div></td><td style="width: 16.96%; vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">21%</font></div></td></tr><tr><td style="width: 83.04%; vertical-align: bottom; background-color: rgb(204, 238, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">After two years but within three years</font></div></td><td style="width: 16.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">5%</font></div></td></tr><tr><td style="width: 83.04%; vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total</font></div></td><td style="width: 16.96%; vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">100%</font></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;">As illustrated above, at March 31, 2019, 95 percent of our available-for-sale securities had a maturity of less than two years.</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">All of our available-for-sale 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.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At March 31, 2019, we had an ownership interest of less than 20 percent in four private companies and two public companies with which we conduct business. The privately-held companies are Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd. 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">94,603</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(34</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">94,603</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(34</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 30%; padding-bottom: 2px; background-color: rgb(255, 255, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Debt securities issued by states of the U.S. and political subdivisions of the states</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">39</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">11,254</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(9</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">51,579</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(319</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">62,833</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(328</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 30%; padding-bottom: 4px; background-color: rgb(204, 238, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total temporarily impaired securities</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">353</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">727,648</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(430</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">170,928</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(926</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">898,576</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1,356</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td></tr></table><div><br /></div></div><span></span>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for investments, including all tables.</p></div>
<a href="javascript:void(0);" onclick="top.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-X (SX)<br> -Number 210<br> -Article 6<br> -Section 10<br> -Paragraph (c)<br> -Subparagraph (1)<br></p></div>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6662643104">
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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">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2019</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueDisclosuresTextBlock', window );">Fair Value Measurements</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4.&#160; Fair Value Measurements</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1, defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly-held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify the majority of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following tables present the major security types we held at March 31, 2019 and December 31, 2018 that we regularly measure and carry at fair value. At March 31, 2019 and December 31, 2018, </font>our ProQR investment was <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">subject to trading restrictions that extend through the fourth quarter of 2019, as a result we</font> included a lack of marketability discount in valuing this investment,</div><div><br /></div><div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">which is a Level 3 input.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> The amount we owned in ProQR did not change from December 31, 2018 to March 31, 2019. 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text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,609,514</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,349</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td></tr></table><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Included in cash and cash equivalents on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(2) $27.1 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(3)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Included in short-term investments on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(4)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$15.0 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(5)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Included in other current assets on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(6)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$50.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; 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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6825085504">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Operating Leases<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LeasesAbstract', window );"><strong>Operating Leases [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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeasesTextBlock', window );">Operating Leases</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; Operating Leases</div><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing facility. We lease this space under a non-cancelable operating lease with an initial term ending in June 2021 and an option to extend the lease for up to two five-year periods.</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We also lease additional office space and we sublease a portion of this space to Akcea. We lease this space under a non-cancelable operating lease with an initial term ending in June 2023 and an option to extend the lease for one five-year period. The sublease with Akcea is eliminated in our condensed consolidated financial statements.</font></div><div><br /></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea entered into an operating lease agreement for office space located in Boston, Massachusetts for its new corporate headquarters in the second quarter of 2018. The lease commencement date was in August 2018 and Akcea took occupancy in September 2018. Akcea is leasing this space under a non-cancelable operating lease with an initial term ending after 123 months and an option to extend the lease for an additional five-year term. Under the lease agreement, Akcea received a three-month free rent period, which commenced on August 15, 2018, and a tenant improvement allowance up to $3.8 million. Akcea provided the lessor with a letter of credit to secure its obligations under the lease in the initial amount of $2.4 million, to be reduced to $1.8 million on the third anniversary of the rent commencement date and to $1.2 million on the fifth anniversary of the rent commencement date if Akcea meets certain conditions set forth in the lease at each such time.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases we did not include the extension options for these leases.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; 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text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 18.7pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Imputed interest</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(7,020</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; 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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for operating leases of lessee. Includes, but is not limited to, description of operating lease and maturity analysis of operating lease liability.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -URI http://asc.fasb.org/subtopic&amp;trid=77888251<br></p></div>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes<br></strong></div></th>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxDisclosureAbstract', window );"><strong>Income Taxes [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="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxDisclosureTextBlock', window );">Income Taxes</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: left; text-indent: -45pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6.&#160; Income Taxes</div><div><br /></div><div style="text-align: justify; text-indent: 24.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our effective tax rate may vary from the U.S. federal statutory tax rate due to the change in the mix of earnings in tax jurisdictions with different statutory rates, benefits related to tax credits, and the tax impact of non-deductible expenses and other permanent differences between income before income taxes and taxable income.&#160; Our effective income tax rate of 25.5 percent for the three months ended March 31, 2019 differed from the U.S. federal statutory rate of 21 percent primarily due to state taxes, partially offset by the tax benefit related to estimated research &amp; development and orphan drug credits and the excess tax benefit related to share-based compensation.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recorded income tax expense of $31 million for the three months ended March 31, 2019, compared to $15,000 </font>for the same period in 2018. The increase in our income tax expense was primarily due to our expectation that we will generate U.S. federal and state taxable income in 2019. Our 2019 income tax expense has two components. The first component relates to federal income taxes. We expect to utilize our deferred tax assets to offset our U.S. federal taxable income. We are recording non-cash income tax expense as we utilize our federal deferred tax assets.&#160;The other component of our income tax expense relates to the estimated cash taxes we will pay for our state income taxes. Although we are recording the expense for our state income taxes in 2019, we will not have to make the majority of the payment for this liability until the first quarter of 2020.</font></div><div><br /></div></div><span></span>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for income taxes. Disclosures may include net deferred tax liability or asset recognized in an enterprise's statement of financial position, net change during the year in the total valuation allowance, approximate tax effect of each type of temporary difference and carryforward that gives rise to a significant portion of deferred tax liabilities and deferred tax assets, utilization of a tax carryback, and tax uncertainties information.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -URI http://asc.fasb.org/topic&amp;trid=2144680<br></p></div>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6825057856">
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<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">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2019</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndLicensingAgreementsAbstract', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CollaborativeArrangementDisclosureTextBlock', window );">Collaborative Arrangements and Licensing Agreements</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div><br /></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7.&#160; Collaborative Arrangements and Licensing Agreements</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Below, we have included our collaborations with substantive changes during the first three months of 2019 from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2018.</font></div><div><br /></div><div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Strategic Partnership</font></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;">Biogen</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. In</font> December 2017, we entered into a collaboration with Biogen to identify <font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense medicines for the treatment of SMA</font>. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, we and Biogen are currently developing six other medicines to treat neurodegenerative diseases under these collaborations, including tofersen (formerly IONIS-SOD1</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">) for ALS patients with SOD1 mutations, or SOD1-ALS, which Biogen moved into a Phase 3 study in the first quarter of 2019, IONIS-MAPT</font><sub>Rx </sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for Alzheimer&#8217;s disease</font><sub>,</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> IONIS-C9</font><sub>Rx </sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for ALS patients with C9ORF72 mutations, and IONIS-BIIB6</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, IONIS-BIIB7</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and IONIS-BIIB8</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to treat undisclosed neurodegenerative diseases. In addition to these medicines, we and Biogen are evaluating numerous additional targets to develop medicines to treat neurological diseases. In April 2018, we entered into a new strategic collaboration for the treatment of neurological diseases with Biogen. From inception through March 2019, we have received over $2.1 billion from our Biogen collaborations, including $1 billion we received from Biogen in the second quarter of 2018 for our 2018 strategic neurology collaboration.</font></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA royalties (commercial revenue)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; 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font-family: 'Times New Roman', Times, serif;">41.1</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D revenue</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">24.5</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">10.8</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; 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width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">51.9</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Percentage of total revenue</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">28</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">36</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></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;">During the first quarter of 2019, we did not have any changes to our performance obligations or the timing in which we expect to recognize revenue under our Biogen collaborations.</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In April 2019, we achieved a $7.5 million milestone payment from Biogen, when we advanced a new target for an unidentified neurological disease<sub>&#160;</sub>under the 2018 strategic neurology collaboration. We will achieve the next payment of up to $10 million if Biogen designates a target under our 2018 strategic neurology collaboration.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our condensed consolidated balance sheet at March 31, 2019 and <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, 2018 </font>included deferred revenue of $556.4 million and $580.9 million, respectively, related to our relationship with Biogen.</font></div><div><br /></div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Commercialization Partners</div><div><br /></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;">Roche</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have two collaborations with Roche, one to develop treatments for Huntington's disease, or HD, and one to </font><font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">develop IONIS-FB-L</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;for the treatment of complement-mediated diseases. In December 2017, upon completion of the Phase 1/2 study of IONIS-HTT</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Roche exercised its option to license IONIS-HTT</font><sub>Rx </sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">and is now responsible for the global development, regulatory and commercialization activities for IONIS-HTT</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In October 2018, we entered into a collaboration agreement with Roche to</font><font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;for the treatment of complement-mediated diseases. The first indication we plan to pursue is the treatment of patients with geographic atrophy, or GA, the advanced stage of dry age-related macular degeneration, or AMD. We are responsible for conducting a Phase 2 study in patients with dry AMD. In addition, we plan to evaluate the medicine for a severe and rare renal indication.&#160;</font>Roche<font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;has the option to license IONIS-FB-L</font><sub><font style="background-color: #FBFBFB;">Rx</font></sub><font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;at the completion of these studies. Upon licensing,&#160;</font>Roche <font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will be responsible for all further global development, regulatory and commercialization activities and costs.</font>&#160;<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through March 2019, we have received over $220 million from our Roche collaborations, including $35 million in </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">milestone payments we earned in the first quarter of 2019 when Roche dosed the first patient in a Phase 3 study for IONIS-HTT</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We will achieve the next payment of $15 million if Roche advances IONIS-HTT</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</font></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D revenue</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">41.2</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2.0</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Percentage of total revenue</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">14</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; 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font-size: 10pt;">Our revenue in the first quarter of 2019, included $35 million of milestone payments we earned when Roche dosed the first patient in the Phase 3 study of IONIS-HTT<sub>Rx</sub>. We recognized these milestone payments in full in the first quarter of 2019 because we do not have any performance obligations related to these milestone payments as Roche is conducting the Phase 3 study of IONIS-HTT<sub>Rx</sub>.</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">During the first quarter of 2019, we did not have any changes to our performance obligations or the timing in which we expect to recognize revenue under our Roche collaborations.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our condensed consolidated balance sheet at March 31, 2019 and <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, 2018 </font>included deferred revenue of $67.5 million and $72.6 million, respectively, related to our relationship with Roche.</font></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;">Akcea Collaboration</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following collaboration agreement relates to Akcea, our majority owned affiliate. 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<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8.&#160; Segment Information</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have two reportable segments Ionis Core and Akcea Therapeutics. </font>At <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">March 31, 2019 </font>we owned approximately 76 percent of Akcea.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.</font></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In our Ionis Core segment we are exploiting our antisense technology to generate a broad pipeline of first-in-class and/or best-in-class medicines for us and our partners. 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text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">March 31, 2019</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3,112,235</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">458,717</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; 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text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,835,889</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, 2018</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,975,491</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">365,261</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(672,968</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2,667,784</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td></tr></table><div><br /></div></div><span></span>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for reporting segments including data and tables. Reportable segments include those that meet any of the following quantitative thresholds a) it's reported revenue, including sales to external customers and intersegment sales or transfers is 10 percent or more of the combined revenue, internal and external, of all operating segments b) the absolute amount of its reported profit or loss is 10 percent or more of the greater, in absolute amount of 1) the combined reported profit of all operating segments that did not report a loss or 2) the combined reported loss of all operating segments that did report a loss c) its assets are 10 percent or more of the combined assets of all operating segments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -URI http://asc.fasb.org/topic&amp;trid=2134510<br></p></div>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6832699904">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basis of Presentation (Policies)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2019</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Basis of Presentation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 months ended March 31, 2019 and 2018 on the same basis as the audited financial statements for the year ended December 31, 2018. 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. Results for the interim periods are not necessarily indicative of the results 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, 2018 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConsolidationPolicyTextBlock', window );">Consolidation</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals,&#160;Inc. and the consolidated results of our majority owned affiliate,&#160;Akcea Therapeutics, Inc. and its wholly owned subsidiaries. We formed Akcea in December 2014. </font>In July 2017, Akcea completed an <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">initial public offering, or IPO,</font> and therefore, beginning in July 2017, we no longer owned 100 percent of Akcea. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub>, increasing our ownership to approximately 76 percent at March 31, 2019. We reflected the increase in our ownership in these financial statements. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Refer to the section titled &#8220;Noncontrolling Interest in Akcea&#8221; in Note 2, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies,</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for further information related to our accounting for our investment in Akcea.</font></div><div><br /></div></div><span></span>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy regarding (1) the principles it follows in consolidating or combining the separate financial statements, including the principles followed in determining the inclusion or exclusion of subsidiaries or other entities in the consolidated or combined financial statements and (2) its treatment of interests (for example, common stock, a partnership interest or other means of exerting influence) in other entities, for example consolidation or use of the equity or cost methods of accounting.  The accounting policy may also address the accounting treatment for intercompany accounts and transactions, noncontrolling interest, and the income statement treatment in consolidation for issuances of stock by a subsidiary.</p></div>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6835321136">
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<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">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2019</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccountingPoliciesAbstract', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerPolicyTextBlock', window );">Revenue Recognition</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><font style="background-color: #FFFFFF;">Revenue Recognition</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Our Revenue Sources</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts in deferred revenue on our consolidated balance sheet.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Commercial Revenue: TEGSEDI Product Sales, net</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018. </font>In the U.S., TEGSEDI is distributed through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients. In Germany, TEGSEDI is distributed through a non-exclusive distribution model with a 3PL that takes title to TEGSEDI. The 3PL is our sole customer in Germany. The 3PL in Germany then distributes TEGSEDI to hospitals and pharmacies.</font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Research and development revenue under collaborative agreements</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We often 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.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We provide details about our collaboration agreements in Note 7, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements,</font> in our Annual Report on Form 10-K for the year ended December 31, 2018<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">.</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</font>Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Steps to Recognize Revenue</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:</font></div><div><br /></div><div><br /></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">1.</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Identify the contract</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</font></div><div><br /></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We and our partner approved the contract and we are both committed to perform our obligations;</font></div></td></tr></table></div></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have identified our rights, our partner&#8217;s rights and the payment terms;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and</font></div></td></tr></table></div></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We believe collectability is probable.</font></div></td></tr></table></div></div><div style="margin-bottom: 10pt;"><br /></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">2.</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Identify the performance obligations</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We next identify the distinct goods and services we are required to provide under the contract. Accounting rules refer to these as our performance obligations. We typically have only one performance obligation at the inception of a contract, which is to perform R&amp;D services.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Often times we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights. These items are contingent upon future events that may not occur. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">3.</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Determine the transaction price</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and are usually based on scientific progress. For example, in the first quarter of 2019, we earned $35 million in milestone payments from Roche when it dosed the first patient in the Phase 3 study of IONIS-HTT<sub>Rx </sub>(RG6042) <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">because we do not have any performance obligations related to these milestone payments as Roche is conducting the Phase 3 study of IONIS-HTT</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</font> At December 31, 2018, we determined it was not probable that we could earn these milestone payments.&#160;As such, we did not recognize any revenue associated with the milestone payments in 2018.</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">4.</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Allocate the transaction price</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Estimated future product sales;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Estimated royalties on future product sales;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Contractual milestone payments;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Expenses we expect to incur;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Income taxes; and</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">A discount rate.</font></div></td></tr></table></div></div><div><br /></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The number of internal hours we estimate we will spend performing these services;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The estimated cost of work we will perform;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The estimated cost of work that we will contract with third parties to perform; and</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The estimated cost of API we will use.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">5.</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Recognize revenue</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</font></font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize royalty revenue in the period in which the counterparty sells the related product, which in certain cases may require us to estimate our royalty revenue. </font>We recognize royalties from SPINRAZA sales in the period Biogen records the sale of SPINRAZA.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Commercial Revenue: TEGSEDI Product Sales, net</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize TEGSEDI product sales in the period </font>when our customer obtains control of TEGSEDI, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative expenses in our condensed consolidated statements of operations. Otherwise payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues, taxes collected from customers relating to product sales and remitted to governmental authorities.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Reserves for TEGSEDI Product Sales</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We record TEGSEDI product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates, co-pay assistance and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as reductions of accounts receivable when the amount is payable to our customer or a current liability when the amount is payable to a party other than our customer in our condensed consolidated balance sheet. In certain cases, our estimates include a range of possible outcomes that are probability-weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net TEGSEDI product sales in the respective period.</font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following are the components of variable consideration related to TEGSEDI product sales:</font></div><div><br /></div><div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Chargebacks: </font>In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We record reserves for these chargebacks related to TEGSEDI product sales to our U.S. customer during the reporting period. We also estimate the amount of product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods.</font></div><div><br /></div><div><br /></div><div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Government rebates</font>: We are subject to discount obligations under government programs, including Medicaid programs and Medicare in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability-weighted for the estimated payer mix. We record these reserves as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments.</font></div><div><br /></div><div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Trade discounts and allowances: </font>We provide customary invoice discounts on TEGSEDI product sales to our U.S. customer for prompt payment. We record this discount as a reduction of TEGSEDI product sales in the period in which we recognize the related product revenue. In addition, we receive and pay for various distribution services from our U.S. customer and wholesalers in our U.S. distribution channel. For services we receive that are either not distinct from the sale of TEGSEDI or for which we cannot reasonably estimate the fair value, we classify such fees as a reduction of TEGSEDI product sales.</font></div><div><br /></div><div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Product Returns: </font>Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the TEGSEDI&#8217;s expiration date. We estimate the amount of TEGSEDI product sales that our customer may return. We record our return estimate as an accrued refund liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales, in the same period we recognize the related sale. Based on our distribution model for TEGSEDI, contractual inventory limits with our customer and wholesalers and the price of TEGSEDI, we believe we will have minimal returns. Our customer in Germany only takes title to the product once it receives an order from a hospital or pharmacy and therefore does not maintain any inventory of TEGSEDI, as such we do not estimate returns in Germany.</font></div><div><br /></div><div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Other incentives: </font>In the U.S., we estimate reserves for other incentives including co-payment assistance we provide to patients with commercial insurance who have coverage and reside in states that allow co-payment assistance. We record a reserve for the amount we estimate we will pay for co-payment assistance. We base our reserve on the number of estimated claims and our estimate of the cost per claim related to TEGSEDI product sales that we have recognized as revenue. We record our other incentive reserve estimates as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our TEGSEDI product sales, in the same period we recognize the related sale.</font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Research and development revenue under collaboration agreements:</u></font></div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Upfront Payments</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we enter into a collaboration agreement with an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. For example, under our <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">collaboration agreement with Roche to</font><font style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;for the treatment of complement-mediated diseases</font>, we received a $75 million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $75 million upfront payment using an input method over the estimated period of time we are providing R&amp;D services.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>Milestone Payments</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because there is considerable uncertainty in the research and development processes that trigger these payments under our collaboration agreements. 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 we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the third quarter of 2017, we initiated a Phase 1/2a clinical study of IONIS-MAPT<sub>Rx </sub>in patients with mild Alzheimer&#8217;s disease. We earned a $10 million milestone payment from Biogen related to the initiation of this study. We added this payment to the transaction price and allocated it to our R&amp;D services performance obligation. We are recognizing revenue from this milestone payment over our estimated period of performance.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the first quarter of 2019, we recognized $35 million in milestone payments <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">when Roche dosed the first patient in a Phase 3 study for IONIS-HTT</font><sub>Rx</sub>. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We concluded that the milestone payments were not related to our R&amp;D services performance obligation. Therefore, we recognized these milestone payments in full in the first quarter of 2019.</font></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-style: italic; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>License Fees</u></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generally recognize as revenue the total amount we determine to be the stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. </font>For example, in the first quarter of 2019, we earned a $150 million license fee when Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub> from us.</font></div><div><br /></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Amendments to Agreements</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If the goods and/or services are at a stand-alone selling price.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and at their stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the prevention of thrombosis. As part of the agreement, Bayer paid us a $100 million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and to initiate development of IONIS-FXI-L</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $75 million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and IONIS-FXI-L</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the 2017 amendment, we concluded we had a new agreement with three performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L</font><sub>Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, to provide R&amp;D services and to deliver API. We allocated the $75 million transaction price to these performance obligations. </font>Refer to <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 7, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</font>, for further discussion <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">of our accounting treatment for our Bayer collaboration.</font></font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">Multiple Agreements</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Whether the agreements were negotiated together with a single objective;</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Whether the goods and/or services promised under the agreements are a single performance obligation.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis.</font></font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ReceivablesPolicyTextBlock', window );">Contracts Receivable</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contract receivable to be unconditional. We typically receive payment within one quarter of billing our partner or customer</font>.</font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy', window );">Unbilled SPINRAZA Royalties</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled SPINRAZA Royalties</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen for SPINRAZA royalties. We include these unbilled amounts in other current assets on our condensed consolidated balance sheet.</font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueRecognitionPolicyTextBlock', window );">Deferred Revenue</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue on our condensed consolidated balance sheet.</font> During the three months ended March 31, 2019 and 2018, we recognized $40.3 million and $34.9 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.</font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostOfSalesPolicyTextBlock', window );">Cost of Products Sold</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div><br /></div><div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Products Sold</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our cost of products sold includes manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of TEGSEDI. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of products sold. Prior to obtaining regulatory approval in July 2018, we expensed a significant portion of the costs we incurred to produce the TEGSEDI supply we are using in the commercial launch as research and development expense. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We previously recognized $0.3 million of costs to produce TEGSEDI related to the TEGSEDI commercial revenue we recognized in the</font> three months ended March 31, 2019.</font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy', window );">Noncontrolling Interest in Akcea Therapeutics, Inc.</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Prior to Akcea&#8217;s IPO in July 2017, we owned 100 percent of Akcea. From the closing of Akcea&#8217;s IPO in July 2017 through mid-April 2018, we owned approximately 68 percent<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font>of Akcea. In the second, third and fourth quarters of 2018, we received additional shares of Akcea&#8217;s stock related to our license of TEGSEDI and AKCEA-TTR-L<sub>Rx</sub> to Akcea, increasing our ownership percentage to approximately 75 percent. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub>, increasing our ownership to approximately 76 percent at March 31, 2019. We reflected this increase in our ownership percentage in these financial statements as an adjustment to noncontrolling interest. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The shares third parties own represent an interest in Akcea&#8217;s equity that is not controlled by us. However, as we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our condensed consolidated financial statements. We reflect the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock in a separate line on the statement of operations and a separate line within stockholders&#8217; equity in our condensed consolidated balance sheet. In addition, we record a noncontrolling interest adjustment to account for the stock options Akcea grants, which if exercised, will dilute our ownership in Akcea. This adjustment is a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized.</font></font></div><div><br /></div></div><span></span>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock', window );">Cash, Cash Equivalents and Investments</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, cash equivalents and investments</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments. We use the specific identification method to determine the cost of securities sold.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At March 31, 2019, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in four privately-held companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd.</font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryPolicyTextBlock', window );">Inventory Valuation</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventory valuation</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or market value under the first-in, first-out method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials they have alternative future uses. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency.</font></div><div style="text-align: justify;"><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We obtained the first regulatory approval for TEGSEDI in July 2018. At March 31, 2019 and December 31, 2018, our physical inventory for TEGSEDI included API that we produced prior to when we obtained regulatory approval and accordingly has no cost basis as we had previously expensed the costs as R&amp;D expenses.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We did not record any inventory write-offs for the three months ended March 31, 2019 and 2018. Total inventory was $11.1 million and $8.6 million as of </font>March 31, 2019 and December 31, 2018<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively.</font></font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeLeasesPolicyTextBlock', window );">Leases</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Leases</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Topic 842 Adoption</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In February 2016, the FASB issued amended accounting guidance related to lease accounting. This guidance supersedes the lease requirements we previously followed in Accounting Standards Codification, or ASC, Topic 840, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</font>, or Topic 840, and created a new lease accounting standard, Topic 842, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</font>, or Topic 842. Under Topic 842, an entity will record on its balance sheet all leases with a term longer than one year. Further, an entity will record a liability with a value equal to the present value of payments it will make over the life of the lease (lease liability) and an asset representing the underlying leased asset (right-of-use asset). The new accounting guidance requires entities to determine if its leases are operating or financing leases. Entities will recognize expense for operating leases on a straight-line basis as an operating expense. If an entity determines a lease is a financing&#160;lease, it will record</font></div><div><br /></div><div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. We adopted Topic 842 on January 1, 2019 and adjusted our opening balance sheet on that date for our right-of-use operating lease assets and operating lease liabilities. At adoption, we recorded $13.5 million in right-of-use operating lease assets and $18.5 million in operating lease liabilities, of which we classified $2 million as a current liability. We adopted Topic 842 using the available practical expedients<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> permitted under the transition guidance within the new standard, which among other things, allowed us to carry forward the historical lease classification of those leases we had in place as of January 1, 2019. </font>The adoption did not have an impact on our condensed consolidated statement of operations.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed consolidated balance sheet for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we will pay over the lease term.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</font>We determined the lease term at the commencement date of the lease, and in certain cases our lease term could include renewal options if we concluded we were reasonably certain that we will exercise the renewal option.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">As our current leases do not provide an interest rate implicit in the lease, we used our or Akcea&#8217;s incremental borrowing rate, based on the information available on the date we adopted Topic 842 in determining the present value of future payments. Our right-of-use operating lease asset also includes any lease payments we made and excludes any tenant improvement allowances we received. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpensePolicy', window );">Research and Development Expenses</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our condensed consolidated balance sheet and we expense them as the services are provided.</div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IntangibleAssetsFiniteLivedPolicy', window );">Patent Expenses</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the United States Patent and Trademark Office, or foreign equivalent, issues the patent. We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. We evaluate patents and patent applications that we are not actively pursuing and write off any associated costs.</div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxPolicyTextBlock', window );">Income Taxes</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act of 2017, or the Tax Act. The Tax Act created a new requirement on global intangible low-taxed income, or GILTI, earned by foreign subsidiaries for tax years beginning on or after January 1, 2018. The GILTI provisions require foreign subsidiary earnings in excess of an allowable return on the foreign subsidiary&#8217;s assets to be included in our U.S. income tax return. Under U.S. GAAP, we are permitted to make an accounting policy election to either treat taxes due on future inclusions in U.S. taxable income related to GILTI as a current-period expense when incurred or to factor such amounts into our measurement of deferred taxes. We have made the election to account for GILTI as a component of current taxes incurred rather than as a component of deferred taxes.</font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock', window );">Long-Lived Assets</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Long-lived assets</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We evaluate long-lived assets, which include property, plant and equipment, right-of-use operating lease assets and patent costs acquired from third parties, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.</font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_UseOfEstimates', window );">Use of Estimates</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The preparation of condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States requires 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 those estimates.</font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerSharePolicyTextBlock', window );">Basic and Diluted Net Income (Loss) per Share</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and diluted net income (loss) per share</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Basic net income (loss) per share</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The calculation of total net income (loss) attributable to our common stockholders for the three months ended March 31, 2019 and 2018 considered our net income for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s loss per share by the weighted average shares we owned in Akcea during the period. 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width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">141,537</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.62</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#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;">For the three months ended March 31, 2019, the calculation excluded the 1 percent notes because the effect on diluted earnings per share was anti-dilutive.</div><div><br /></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For the three months ended March 31, 2018, 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:</font></div><div><br /></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1 percent convertible senior notes;</font></div></td></tr></table></div></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Dilutive stock options;</font></div></td></tr></table></div></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Unvested restricted stock units; and</font></div></td></tr></table></div></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Employee Stock Purchase Plan, or ESPP.</font></div></td></tr></table></div></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtPolicyTextBlock', window );">Convertible Debt</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible debt</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for convertible debt instruments that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate. We determine the carrying amount of the liability component by measuring the fair value of similar debt instruments that do not have the conversion feature. If no similar debt instrument exists, we estimate fair value by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities. To determine the fair value of the debt component we are required to use accounting estimates and assumptions. These estimates and assumptions are judgmental in nature and could have a significant impact on the determination of the debt component, and the associated non-cash interest expense.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method.</font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingPolicyPolicyTextBlock', window );">Segment Information</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Segment information</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have two operating segments, our Ionis Core segment and Akcea Therapeutics, our majority-owned affiliate. Akcea is </font>a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We provide segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviews to assess operating performance and to make operating decisions. We allocate a portion of Ionis&#8217; development, R&amp;D support and general and administrative expenses to Akcea for work Ionis performs on behalf of Akcea.</font></font></div><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy', window );">Stock-Based Compensation Expense</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-based compensation expense</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, restricted stock units, or RSUs, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. 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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock', window );">Impact of Recently Issued Accounting Standards</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impact of recently issued accounting standards</div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. The new standard is effective for annual and interim periods beginning after December 15, 2019. Early adoption is permitted for periods beginning after December 15, 2018. When we adopt the new standard, we will make any adjustments to beginning balances through a cumulative-effect adjustment to accumulated deficit on that date. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it will have on our condensed consolidated financial statements and disclosures.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. The updated guidance is effective for fiscal years beginning after December 31, 2019, and interim periods within those fiscal years. Early adoption is permitted in any interim period. We are currently assessing the effects this updated guidance could have on our condensed consolidated financial statements and timing of adoption.</font></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2018, the FASB updated its disclosure requirements related to Level 1, 2 and 3 fair value measurements. The update included deletion and modification of certain disclosure requirements and additional disclosure related to Level 3 measurements. The guidance is effective for fiscal years beginning after December 31, 2019 and early adoption is permitted. We adopted this updated guidance on January 1, 2019 and it did not have a significant impact on our disclosures.</font></div><div><br /></div><div style="text-align: left;"><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we will implement it (in italics):</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 72pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">We will apply all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Adds &#8220;unit of account&#8221; concept to collaboration accounting guidance to align with Topic 606. The &#8220;unit of account&#8221; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 72pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">We will use the &#8220;unit of account&#8221; concept when we receive consideration under a collaboration to determine when we recognize revenue or a contra expense</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">3)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties</font></div></td></tr></table></div></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 72pt;"></td><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#9679;</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we will not recognize revenue for the transaction</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The updated guidance is effective for public entities for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. Early adoption is permitted. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it will have on our condensed consolidated financial statements and disclosures.</font></div><div><br /></div></div><span></span>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for cash, cash equivalents and investments.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for subsidiaries or other investments that are consolidated, including the accounting treatment for intercompany accounts or transactions and any noncontrolling interest.</p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for recognition of costs in the period which correspond to the sales and revenue categories presented in the statement of operations. The accounting policy may include the amount and nature of costs incurred, provisions associated with inventories, purchase discounts, freight and other costs included in cost of sales incurred and recorded in the period. This disclosure also includes the nature of costs of sales incurred and recorded in the statement of operations for the period relating to transactions with related parties.</p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy related to debt. Includes, but is not limited to, debt issuance costs, the effects of refinancings, method of amortizing debt issuance costs and original issue discount, and classifications of debt.</p></div>
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<a href="javascript:void(0);" onclick="top.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>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for the impairment and disposal of long-lived assets including goodwill and other intangible assets.</p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for income taxes, which may include its accounting policies for recognizing and measuring deferred tax assets and liabilities and related valuation allowances, recognizing investment tax credits, operating loss carryforwards, tax credit carryforwards, and other carryforwards, methodologies for determining its effective income tax rate and the characterization of interest and penalties in the financial statements.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32847-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 954<br> -SubTopic 740<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6491622&amp;loc=d3e9504-115650<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 17<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32809-109319<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32840-109319<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -URI http://asc.fasb.org/extlink&amp;oid=84176650&amp;loc=d3e32247-109318<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI http://asc.fasb.org/extlink&amp;oid=84176650&amp;loc=d3e32280-109318<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 30<br> -Section 05<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=65884525&amp;loc=d3e40913-109327<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for finite-lived intangible assets. This accounting policy also might address: (1) the amortization method used; (2) the useful lives of such assets; and (3) how the entity assesses and measures impairment of such assets.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of inventory accounting policy for inventory classes, including, but not limited to, basis for determining inventory amounts, methods by which amounts are added and removed from inventory classes, loss recognition on impairment of inventories, and situations in which inventories are stated above cost.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=66092785&amp;loc=d3e4556-108314<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6361739&amp;loc=d3e7789-107766<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 270<br> -SubTopic 10<br> -Section 45<br> -Paragraph 6<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109236672&amp;loc=d3e543-108305<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=66092785&amp;loc=d3e4492-108314<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.6(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for leasing arrangement entered into by lessee.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918666-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for trade and other accounts receivable, and finance, loan and lease receivables, including those classified as held for investment and held for sale. This disclosure may include (1) the basis at which such receivables are carried in the entity's statements of financial position (2) how the level of the valuation allowance for receivables is determined (3) when impairments, charge-offs or recoveries are recognized for such receivables (4) the treatment of origination fees and costs, including the amortization method for net deferred fees or costs (5) the treatment of any premiums or discounts or unearned income (6) the entity's income recognition policies for such receivables, including those that are impaired, past due or placed on nonaccrual status and (7) the treatment of foreclosures or repossessions (8) the nature and amount of any guarantees to repurchase receivables.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(4))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10133-111534<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=84173941&amp;loc=d3e4975-111524<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=6879938&amp;loc=d3e572229-122910<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(3))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for costs it has incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 730<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6420194&amp;loc=d3e21568-108373<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue from contract with customer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18823-107790<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -URI http://asc.fasb.org/topic&amp;trid=49130388<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue recognition. If the entity has different policies for different types of revenue transactions, the policy for each material type of transaction is generally disclosed. If a sales transaction has multiple element arrangements (for example, delivery of multiple products, services or the rights to use assets) the disclosure may indicate the accounting policy for each unit of accounting as well as how units of accounting are determined and valued. The disclosure may encompass important judgment as to appropriateness of principles related to recognition of revenue. The disclosure also may indicate the entity's treatment of any unearned or deferred revenue that arises from the transaction.</p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for segment reporting.</p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for stock option and stock incentive plans. This disclosure may include (1) the types of stock option or incentive plans sponsored by the entity (2) the groups that participate in (or are covered by) each plan (3) significant plan provisions and (4) how stock compensation is measured, and the methodologies and significant assumptions used to determine that measurement.</p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for treatment of receivables that are billable but have not been billed as of the balance sheet date.</p></div>
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<a href="javascript:void(0);" onclick="top.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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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6812245232">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2019</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock', window );">Basic and Diluted Net Income Per Share</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our diluted net income per share for the three months ended March 31, 2019 as follows (in thousands except per share amounts):</div><div><br /></div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three months ended March 31, 2019</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; 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text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">87,543</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">138,582</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; 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background-color: #FFFFFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Shares issuable upon exercise of stock options</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Shares issuable upon restricted stock award issuance</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">665</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Shares issuable related to our ESPP</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">38</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Income available to Ionis common stockholders</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">87,543</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">141,537</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.62</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td></tr></table><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ShareBasedCompensationLineItems', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for Stock Options</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the three months ended March 31, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations:</div><div><br /></div><div style="text-align: left; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Ionis Employee Stock Options:</font></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><tr><td style="width: 70.68%; vertical-align: bottom;">&#160;</td><td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div></td></tr><tr><td style="width: 70.68%; 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vertical-align: bottom; background-color: rgb(204, 238, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2.4%</font></div></td><td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td><td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2.2%</font></div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Dividend yield</font></div></td><td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td><td style="width: 10.66%; 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vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">4.6 years</font></div></td><td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td><td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">4.6 years</font></div></td></tr></table><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for ESPP</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis ESPP:</div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><tr><td style="width: 70.68%; vertical-align: bottom;">&#160;</td><td colspan="5" style="width: 29.32%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom;">&#160;</td><td colspan="2" style="width: 13.37%; vertical-align: bottom; 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font-family: 'Times New Roman', Times, serif;">2.5%</font></div></td><td style="width: 2.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td><td style="width: 2.65%; vertical-align: bottom; background-color: rgb(204, 238, 255);">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: rgb(204, 238, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1.6%</font></div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Dividend yield</font></div></td><td style="width: 2.71%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: right;"><font style="font-size: 10pt; 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font-family: 'Times New Roman', Times, serif;">6 months</font></div></td><td style="width: 2.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td><td style="width: 2.65%; vertical-align: bottom; background-color: rgb(255, 255, 255);">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">6 months</font></div></td></tr></table><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock', window );">Stock-Based Compensation Expense</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 months ended March 31, 2019 and 2018 (in thousands). 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font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Cost of products sold</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">118</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Research, development and patent</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Selling, general and administrative</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">20,952</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">8,769</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">45,505</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">28,451</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td></tr></table><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ShareBasedCompensationLineItems', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for Stock Options</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div><br /></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our stock plans, Akcea has its own stock plan under which it grants options and RSUs and under which it derives its stock-based compensation expense. 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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6611942272">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2019</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentsAbstract', window );"><strong>Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock', window );">Contract Maturity of Available-for-Sale Securities</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 March 31, 2019:</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><tr><td style="width: 83.04%; vertical-align: bottom; background-color: rgb(204, 238, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">One year or less</font></div></td><td style="width: 16.96%; vertical-align: bottom; background-color: rgb(204, 238, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">74%</font></div></td></tr><tr><td style="width: 83.04%; vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">After one year but within two years</font></div></td><td style="width: 16.96%; vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">21%</font></div></td></tr><tr><td style="width: 83.04%; vertical-align: bottom; background-color: rgb(204, 238, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">After two years but within three years</font></div></td><td style="width: 16.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">5%</font></div></td></tr><tr><td style="width: 83.04%; vertical-align: bottom; background-color: rgb(255, 255, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total</font></div></td><td style="width: 16.96%; vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">100%</font></div></td></tr></table><div><br /></div></div><span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock', window );">Summary of Investments</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"></font><br /></div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"></td><td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" rowspan="1" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"></td><td colspan="1" nowrap="nowrap" rowspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Gross Unrealized</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" rowspan="1" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"></td><td colspan="1" nowrap="nowrap" rowspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td></tr><tr><td rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31, 2019</font></div></td><td colspan="1" rowspan="1" valign="bottom" style="vertical-align: bottom; 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text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; 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text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Available-for-sale securities:</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; 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text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total equity securities included in other current assets (3)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,212</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">137</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,349</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total available-for-sale and equity securities</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,874,529</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">556</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(4,068</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,871,017</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td></tr></table><div><br /></div><div style="text-align: left;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; 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font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(3)</font></td><td style="width: auto; vertical-align: top; text-align: left;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize our equity securities at 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 on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div></div><span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock', window );">Temporarily Impaired Investments</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 March 31, 2019. 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. We believe it is more likely than not that we will be able to hold our debt securities to maturity. 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font-weight: bold;">Less than 12 Months of</font></div><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Temporary Impairment</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">More than 12 Months of</font></div><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Temporary Impairment</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; 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font-family: 'Times New Roman', Times, serif; font-weight: bold;">Fair Value</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Unrealized</font></div><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Losses</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; padding-bottom: 2px; width: 1%;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Estimated</font></div><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Fair Value</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; width: 1%;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; width: 1%;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"><div style="text-align: center;"><font style="font-size: 10pt; 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background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; 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padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">11,254</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(9</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">51,579</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(319</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; 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background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(255, 255, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(328</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 30%; padding-bottom: 4px; background-color: rgb(204, 238, 255);"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total temporarily impaired securities</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 6%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">353</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; 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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6824987536">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements (Tables)<br></strong></div></th>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock', window );">Assets Measured at Fair Value on a Recurring Basis</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following tables present the major security types we held at March 31, 2019 and December 31, 2018 that we regularly measure and carry at fair value. At March 31, 2019 and December 31, 2018, </font>our ProQR investment was <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">subject to trading restrictions that extend through the fourth quarter of 2019, as a result we</font> included a lack of marketability discount in valuing this investment,</div><div><br /></div><div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">which is a Level 3 input.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> The amount we owned in ProQR did not change from December 31, 2018 to March 31, 2019. 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width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">79,942</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; 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background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8212;</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,349</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt;"><font style="font-size: 10pt; 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vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">406,435</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,609,514</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1,349</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td></tr></table><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Included in cash and cash equivalents on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(2) $27.1 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</font></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(3)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Included in short-term investments on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(4)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$15.0 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(5)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Included in other current assets on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(6)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$50.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; 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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of assets, including [financial] instruments measured at fair value that are classified in stockholders' equity, if any, by class that are measured at fair value on a recurring basis. The disclosures contemplated herein include the fair value measurements at the reporting date by the level within the fair value hierarchy in which the fair value measurements in their entirety fall, segregating fair value measurements using quoted prices in active markets for identical assets (Level 1), significant other observable inputs (Level 2), and significant unobservable inputs (Level 3).</p></div>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6663832464">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Operating Leases (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2019</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LeasesAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeaseInformationTableTextBlock', window );">Amounts Related to Operating Leases</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">At March 31, 2019</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Right-of-use operating lease assets (1)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">13.1</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Operating lease liabilities (2)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">18.0</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Weighted average remaining lease term</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">9 years</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Weighted average discount rate</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">7.6</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div></td></tr></table><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(1)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Included in deposits and other assets on our condensed consolidated balance sheet.</font></div></td></tr></table></div></div><div><br /></div><div style="text-align: justify;"><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%;"><tr><td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(2)</font></td><td style="width: auto; vertical-align: top; text-align: justify;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Current portion of $2.0 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.</font></div></td></tr></table></div></div><div><br /></div></div><span></span>
</td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock', window );">Future Minimum Payments Under Operating Leases</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2019, the payments for our operating lease liabilities are as follows (in thousands):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</font><font style="font-size: 10pt; 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vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"><div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Years ending December 31,</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; margin-left: 18.7pt;"><font style="font-size: 10pt; 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font-family: 'Times New Roman', Times, serif;">Imputed interest</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(7,020</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">)</font></div></td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 36.7pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total operating lease liabilities</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">17,960</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td></tr></table><div><br /></div></div><span></span>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of information on lessee's operating leases, including carrying value of right-of-use assets and lease liabilities, weighted-average remaining term and weighted-average discount rate.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of future minimum lease payments as of the date of the latest balance sheet presented, in aggregate and for each of the five years succeeding fiscal years, with separate deductions from the total for the amount representing executor costs, including any profit thereon, included in the minimum lease payments and for the amount of the imputed interest necessary to reduce the net minimum lease payments to present value.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 840<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84164817&amp;loc=d3e45280-112737<br></p></div>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6833931328">
<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">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2019</div></th></tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [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="top.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="top.Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA royalties (commercial revenue)</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">59.7</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">41.1</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D revenue</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">24.5</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">10.8</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#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: 27pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total revenue from our relationship with Biogen</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">84.2</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">51.9</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Percentage of total revenue</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">28</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">36</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div></td></tr></table><div><br /></div></div><span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember', 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="top.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="top.Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Three Months Ended</font></div><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">March 31,</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> 2019</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2018</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D revenue</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">41.2</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2.0</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Percentage of total revenue</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">14</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td><td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1</font></div></td><td colspan="1" nowrap="nowrap" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">%</font></div></td></tr></table><div><br /></div></div><span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [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="top.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="top.Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three months ended March 31, 2019 and 2018, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="width: 80%; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</font></div></td><td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center;"><font style="font-size: 10pt; 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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6811976000">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basis of Presentation (Details) - Akcea [Member] - shares<br> shares in Millions</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
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<tr>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
<th class="th"><div>Apr. 30, 2018</div></th>
<th class="th"><div>Jul. 31, 2017</div></th>
<th class="th"><div>Jun. 30, 2017</div></th>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">76.00%<span></span>
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<td class="nump">75.00%<span></span>
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<td class="nump">68.00%<span></span>
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<td class="nump">68.00%<span></span>
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<td class="nump">100.00%<span></span>
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<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ReceiptOfSharesInSubsidiary', window );">Additional shares of Akcea stock received (in shares)</a></td>
<td class="nump">2.8<span></span>
</td>
<td class="text">&#160;<span></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_ReceiptOfSharesInSubsidiary">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of shares received from the subsidiary during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_ReceiptOfSharesInSubsidiary</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_us-gaap_MinorityInterestOwnershipPercentageByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestOwnershipPercentageByParent</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>num: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_ProceedsFromIssuanceOrSaleOfEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract</td>
</tr>
<tr>
<td style="padding-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_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_OwnershipAxis=ions_AkceaTherapeuticsIncMember</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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</html>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6836173888">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Revenue Recognition (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="5">3 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Feb. 28, 2017 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>May 31, 2015 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2019 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2018 </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Mar. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract', window );">Number of performance obligations at inception of contract | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 297,214<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 144,419<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="top.Show.showAR( this, 'defref_srt_MajorCustomersAxis=ions_BiogenIncMember', window );">Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfAgreementsWithCollaborationPartner', window );">Number of agreements | Agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,623<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 942<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember', window );">Roche [Member] | IONIS-HTT [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember', 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>
<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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember', window );">Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPriceAdditions', window );">Milestone payment earned and amortized over period of performance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | 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>
<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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember', window );">Bayer [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></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>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember', window );">Bayer [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember', window );">Bayer [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_NumberOfAgreementsWithCollaborationPartner">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of agreements entered into with the collaboration partner.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfAgreementsWithCollaborationPartner</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of performance obligations at the inception of a contract.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPriceAdditions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The additional amount of consideration the Company earned under the collaboration agreement that is added to the transaction price.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPriceAdditions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130543-203045<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130539-203045<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130545-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_BiogenIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_MajorCustomersAxis=ions_BiogenIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</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_LicensingAndOtherRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember</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_HttMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_HttMember</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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<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember</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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<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_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</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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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</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>
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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_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementsAndLicensingAgreementsBayerMember</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>
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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_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember</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 class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember</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>
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</div></td></tr>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>36
<FILENAME>R26.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6828258848">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Contracts Receivable (Details)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 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="top.Show.showAR( this, 'defref_us-gaap_ContractReceivablesAbstract', window );"><strong>Contracts Receivable [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="top.Show.showAR( this, 'defref_ions_PeriodAfterBillingWhenPaymentIsReceived', window );">Period of time after billing when payment is received</a></td>
<td class="text">3 months<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PeriodAfterBillingWhenPaymentIsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The time period between billing a collaboration partner for goods delivered or services performed that are due unconditionally and payment is received from the collaboration partner, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PeriodAfterBillingWhenPaymentIsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</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_ContractReceivablesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractReceivablesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>37
<FILENAME>R27.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
							function toggleNextSibling (e) {
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</head>
<body>
<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6825017872">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Deferred Revenue (Details) - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityRevenueRecognized', window );">Revenue recognized from amounts in beginning deferred revenue balance</a></td>
<td class="nump">$ 40.3<span></span>
</td>
<td class="nump">$ 34.9<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityRevenueRecognized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of revenue recognized that was previously included in balance of obligation to transfer good or service to customer for which consideration from customer has been received or is due.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityRevenueRecognized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>38
<FILENAME>R28.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
							function toggleNextSibling (e) {
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</head>
<body>
<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6825106960">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Cost of Products Sold (Details)<br> $ in Millions</strong></div></th>
<th class="th">
<div>Mar. 31, 2019 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostOfGoodsAndServicesSoldAbstract', window );"><strong>Cost of Products Sold [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativeCostOfProductsSold', window );">Costs incurred to produce TEGSEDI that were previously recognized</a></td>
<td class="nump">$ 0.3<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativeCostOfProductsSold">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cumulative costs related to goods produced and sold that were previously recognized as expense.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_CumulativeCostOfProductsSold</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostOfGoodsAndServicesSoldAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostOfGoodsAndServicesSoldAbstract</td>
</tr>
<tr>
<td style="padding-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>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>39
<FILENAME>R29.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
							function toggleNextSibling (e) {
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</head>
<body>
<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6815892544">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Noncontrolling Interest in Akcea (Details) - Akcea [Member] - shares<br> shares in Millions</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
<th class="th"><div>Apr. 30, 2018</div></th>
<th class="th"><div>Jul. 31, 2017</div></th>
<th class="th"><div>Jun. 30, 2017</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NoncontrollingInterestAbstract', window );"><strong>Noncontrolling Interest in Akcea Therapeutics, Inc. [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">
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<td class="nump">76.00%<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
</tr>
<tr class="re">
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<td class="nump">2.8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of shares received from the subsidiary during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_ReceiptOfSharesInSubsidiary</td>
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<tr>
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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="top.Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NoncontrollingInterestAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_OwnershipAxis=ions_AkceaTherapeuticsIncMember</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> Period Type:</strong></td>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6632454208">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)<br></strong></div></th>
<th class="th">
<div>Mar. 31, 2019 </div>
<div>Company</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract', window );"><strong>Cash, Cash Equivalents and Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of publicly-held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">2<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="top.Show.showAR( this, 'defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of privately-held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">4<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment</td>
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<td><strong> Data Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6825027776">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Inventory Valuation (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2018</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract', window );"><strong>Inventory Valuation [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>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryWriteDown', window );">Inventory write-off</a></td>
<td class="nump">$ 0<span></span>
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<td class="nump">$ 0<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="top.Show.showAR( this, 'defref_us-gaap_InventoryNet', window );">Inventories</a></td>
<td class="nump">$ 11,057<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 8,582<span></span>
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</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_InventoryNet">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=82887183&amp;loc=d3e6676-107765<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 35<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=68049868&amp;loc=d3e3927-108312<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.6(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract</td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of loss from reductions in inventory due to subsequent measurement adjustments, including, but not limited to, physical deterioration, obsolescence, or changes in price levels.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 35<br> -Paragraph 1B<br> -URI http://asc.fasb.org/extlink&amp;oid=68049868&amp;loc=SL66093879-108312<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.2)<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 35<br> -Paragraph 1C<br> -URI http://asc.fasb.org/extlink&amp;oid=68049868&amp;loc=SL66093883-108312<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=66092785&amp;loc=d3e4542-108314<br></p></div>
<a href="javascript:void(0);" onclick="top.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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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6835292944">
<tr>
<th class="tl" colspan="2" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Leases (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [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="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAsset', window );">Right-of-use operating lease assets</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 13,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Operating lease liabilties</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">17,960<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="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrent', window );">Current portion of operating lease liabilties</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 2,000<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="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsForNewAccountingPronouncementsAxis=us-gaap_AccountingStandardsUpdate201602Member', window );">Topic 842 [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="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAsset', window );">Right-of-use operating lease assets</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 13,500<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Operating lease liabilties</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">18,500<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrent', window );">Current portion of operating lease liabilties</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,000<span></span>
</td>
</tr>
<tr><td colspan="4"></td></tr>
<tr><td colspan="4"><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 deposits and other assets on our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Current portion of $2.0 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.</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_LesseeDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</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_OperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiability</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<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 border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease, classified as current.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_AdjustmentsForNewAccountingPronouncementsAxis=us-gaap_AccountingStandardsUpdate201602Member</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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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6834779968">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Basic and Diluted Net Income (Loss) per Share (Details) - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2018</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="nump">$ 0.63<span></span>
</td>
<td class="num">$ (0.01)<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="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss)</a></td>
<td class="nump">$ 84,443<span></span>
</td>
<td class="num">$ (1,420)<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="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic', window );">Net income (loss) available to Ionis common shareholders</a></td>
<td class="nump">$ 87,543<span></span>
</td>
<td class="num">$ (1,212)<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="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Weighted average shares outstanding (in shares)</a></td>
<td class="nump">138,582<span></span>
</td>
<td class="nump">125,330<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="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted', window );">Income available to Ionis common shareholders, plus assumed conversions</a></td>
<td class="nump">$ 87,543<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="top.Show.showAR( this, 'defref_ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan', window );">Shares issuable related to our ESPP (in shares)</a></td>
<td class="nump">38<span></span>
</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="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net income per share (in shares)</a></td>
<td class="nump">141,537<span></span>
</td>
<td class="nump">125,330<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="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net income per share (in dollars per share)</a></td>
<td class="nump">$ 0.62<span></span>
</td>
<td class="num">$ (0.01)<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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements', window );">Shares issuable related to stock-based compensation (in shares)</a></td>
<td class="nump">2,252<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="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockMember', window );">Restricted Stock Awards [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements', window );">Shares issuable related to stock-based compensation (in shares)</a></td>
<td class="nump">665<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="top.Show.showAR( this, 'defref_us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember', window );">Ionis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss)</a></td>
<td class="nump">$ 63,697<span></span>
</td>
<td class="nump">$ 18,785<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="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss)</a></td>
<td class="nump">$ 23,846<span></span>
</td>
<td class="num">$ (19,997)<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="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | Common Stock [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_WeightedAverageNumberOfSharesOwnedInSubsidiary', window );">Weighted average shares owned in Akcea (in shares)</a></td>
<td class="nump">68,582<span></span>
</td>
<td class="nump">45,448<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="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="nump">$ 0.35<span></span>
</td>
<td class="num">$ (0.44)<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="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss)</a></td>
<td class="nump">$ 23,846<span></span>
</td>
<td class="num">$ (19,997)<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_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of shares issuable related to employee stock purchase plan.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan</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_WeightedAverageNumberOfSharesOwnedInSubsidiary">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares owned in the subsidiary during the reporting period determined by relating the portion of time within a reporting period that shares have been owned to the total time in that period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_WeightedAverageNumberOfSharesOwnedInSubsidiary</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_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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_EarningsPerShareBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873790&amp;loc=SL114874131-224263<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1337-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI http://asc.fasb.org/extlink&amp;oid=109256448&amp;loc=d3e4984-109258<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(21))<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1252-109256<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873765&amp;loc=SL114874048-224260<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=SL5780133-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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_EarningsPerShareBasicAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareBasicAbstract</td>
</tr>
<tr>
<td style="padding-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_EarningsPerShareDiluted">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI http://asc.fasb.org/extlink&amp;oid=109256448&amp;loc=d3e4984-109258<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1252-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873765&amp;loc=SL114874048-224260<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1337-109256<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(21))<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=SL5780133-109256<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873790&amp;loc=SL114874131-224263<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of share based payment arrangements using the treasury stock method.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28A<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1500-109256<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements</td>
</tr>
<tr>
<td style="padding-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_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669619-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873765&amp;loc=SL114874048-224260<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL7669625-108580<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(18))<br> -URI http://asc.fasb.org/extlink&amp;oid=114873790&amp;loc=SL114874131-224263<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3602-108585<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities; of income (loss) available to common shareholders.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1377-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic</td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities, and addition from assumption of issuance of common shares for dilutive potential common shares; of income (loss) available to common shareholders.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1505-109256<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1377-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted</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><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1505-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=109260490&amp;loc=d3e1448-109256<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfSharesOutstandingBasic</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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> 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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6665675984">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Segment Information (Details)<br></strong></div></th>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of operating segments. An operating segment is a component of an enterprise: (a) that engages in business activities from which it may earn revenues and incur expenses (including revenues and expenses relating to transactions with other components of the same enterprise), (b) whose operating results are regularly reviewed by the enterprise's chief operating decision maker to make decisions about resources to be allocated to the segment and assess its performance, and (c) for which discrete financial information is available. An operating segment may engage in business activities for which it has yet to earn revenues, for example, start-up operations may be operating segments before earning revenues.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<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>45
<FILENAME>R35.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6822340096">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Stock-Based Compensation Expense (Details) - USD ($)<br> $ / shares in Units, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 45,505<span></span>
</td>
<td class="nump">$ 28,451<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [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="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">2.40%<span></span>
</td>
<td class="nump">2.20%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">60.30%<span></span>
</td>
<td class="nump">63.20%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">4 years 7 months 6 days<span></span>
</td>
<td class="text">4 years 7 months 6 days<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions', window );">Unrecognized compensation expense related to non-vested stock options</a></td>
<td class="nump">$ 192,200<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="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">1 year 4 months 24 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">2.50%<span></span>
</td>
<td class="nump">1.60%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">45.50%<span></span>
</td>
<td class="nump">44.40%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></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="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract', window );"><strong>Stock-based Compensation Expense [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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<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="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested RSUs</a></td>
<td class="nump">$ 68,700<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="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">2 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract', window );"><strong>Stock-based Compensation Expense [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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share)</a></td>
<td class="nump">$ 58.26<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="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember', window );">Cost of Products Sold [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="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 118<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="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentMember', window );">Research, Development and Patent [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="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">24,435<span></span>
</td>
<td class="nump">19,682<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember', window );">Selling, General and Administrative [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="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">20,952<span></span>
</td>
<td class="nump">8,769<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [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="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 18,600<span></span>
</td>
<td class="nump">$ 6,400<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | Employee Stock Options [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="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">2.50%<span></span>
</td>
<td class="nump">2.60%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">76.40%<span></span>
</td>
<td class="nump">77.10%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">6 years 1 month 6 days<span></span>
</td>
<td class="text">6 years 1 month 6 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="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | ESPP [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="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">2.50%<span></span>
</td>
<td class="nump">1.60%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">64.10%<span></span>
</td>
<td class="nump">62.30%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">6 months<span></span>
</td>
<td class="text">6 months<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_AllocatedShareBasedCompensationExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Represents the expense recognized during the period arising from equity-based compensation arrangements (for example, shares of stock, unit, stock options or other equity instruments) with employees, directors and certain consultants qualifying for treatment as employees.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5047-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.F)<br> -URI http://asc.fasb.org/extlink&amp;oid=115993241&amp;loc=d3e301413-122809<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (h)(1)(i)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract</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> 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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Weighted average period over which unrecognized compensation is expected to be recognized for equity-based compensation plans, 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Unrecognized cost of unvested share-based awards, other than options, awarded to employees as compensation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Unrecognized cost of unvested options awarded to employees as compensation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Period which an employee's right to exercise an award is no longer contingent on satisfaction of either a service condition, market condition or a performance condition, 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iii)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iv)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Weighted average expected volatility rate of share-based compensation awards.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Expected term of share-based compensation awards, 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(i)<br> -URI http://asc.fasb.org/extlink&amp;oid=109197908&amp;loc=d3e5070-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.D.2)<br> -URI http://asc.fasb.org/extlink&amp;oid=115993241&amp;loc=d3e301413-122809<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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</tr>
<tr>
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<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember</td>
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<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>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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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_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_RelatedPartyTransactionsByRelatedPartyAxis=ions_EmployeeMember</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_ResearchDevelopmentAndPatentMember</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember</td>
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<tr>
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<td style="white-space:nowrap;">srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</td>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6823213152">
<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">3 Months Ended</th>
</tr>
<tr><th class="th">
<div>Mar. 31, 2019 </div>
<div>Company</div>
</th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage', window );">One year or less</a></td>
<td class="nump">74.00%<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="top.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="top.Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage', window );">After two years but within three years</a></td>
<td class="nump">5.00%<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="top.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="top.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">95.00%<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="top.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="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange3', window );">Maximum contract maturity period, range 3</a></td>
<td class="text">3 years<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_invest_InvestmentsScheduleAbstract', window );"><strong>Ownership Interests in Private and Public Companies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of privately-held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">4<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="top.Show.showAR( this, 'defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of publicly-held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">2<span></span>
</td>
</tr>
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<div style="display: none;">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">invest_InvestmentsScheduleAbstract</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_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature beyond two years but within three years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage</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_ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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> Data Type:</strong></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_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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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>
<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>num: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_MaximumContractMaturityPeriodRange1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange2">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange2</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange3">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_AvailableForSaleSecuritiesDebtMaturitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</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>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>47
<FILENAME>R37.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6835847264">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Investments, Summary of Investments (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th" colspan="2"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,212<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 1,212<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedGain', 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="fn" style="border-bottom: 0px;"></td>
<td class="nump">137<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(244)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">968<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,349<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="top.Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNICost', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,920,577<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,874,529<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="top.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">2,045<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">556<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="top.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">(1,600)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(4,068)<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="top.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">1,921,022<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,871,017<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember', window );">Available-for-sale 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">1,919,365<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,873,317<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">2,045<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">419<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(1,356)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(4,068)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">1,920,054<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,869,668<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember', window );">Available-for-sale Securities [Member] | Securities with Maturity of One Year or Less [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">1,388,864<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,433,930<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">518<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">31<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(761)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(2,362)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">1,388,621<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,431,599<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember', window );">Available-for-sale Securities [Member] | Securities with Maturity of More than One Year [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">530,501<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">439,387<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">1,527<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">388<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(595)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(1,706)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">531,433<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">438,069<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member] | Securities with Maturity of One Year or Less [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">869,483<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">956,879<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">326<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">13<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(531)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(1,858)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">869,278<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">955,034<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member] | Securities with Maturity of More than One Year [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">360,976<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">299,018<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">1,236<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">194<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(336)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(1,286)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">361,876<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">297,926<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of One Year or Less [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">124,744<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">168,839<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">71<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">3<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(15)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(104)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">124,800<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">168,738<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of More than One Year [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">120,341<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">107,789<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">279<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">194<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(112)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(109)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">120,508<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">107,874<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities issued by the U.S. Treasury [Member] | Securities with Maturity of One Year or Less [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">328,340<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">244,640<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">110<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">15<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(12)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(77)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">328,438<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">244,578<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities issued by the U.S. Treasury [Member] | Securities with Maturity of More than One Year [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">33,569<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">15,600<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">12<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(22)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(24)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">33,559<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">15,576<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of One Year or Less [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1],[2]</sup></td>
<td class="nump">63,366<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">63,572<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">10<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(203)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(323)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">63,173<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">63,249<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of More than One Year [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">15,615<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">16,980<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(125)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(287)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">15,490<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 16,693<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember', window );">Other Municipal Debt Securities [Member] | Securities with Maturity of One Year or Less [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">2,931<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="top.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">1<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="top.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="nump">0<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="top.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">$ 2,932<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="5"></td></tr>
<tr><td colspan="5"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Our available-for-sale securities are held at amortized cost.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Includes investments classified as cash equivalents on our condensed consolidated balance sheet.</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_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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<td>instant</td>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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</div></td></tr>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=82897076&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=82897076&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Data Type:</strong></td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
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</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_AvailableForSaleDebtSecuritiesAmortizedCostBasis">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=82897076&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109979856&amp;loc=d3e26610-111562<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -URI http://asc.fasb.org/extlink&amp;oid=82897076&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td style="padding-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>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=99377092&amp;loc=SL75136599-209740<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>debit</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_EquitySecuritiesFvNiUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 321<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=84241550&amp;loc=SL75117546-209714<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 321<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=84241550&amp;loc=SL75117546-209714<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember</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>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfOneYearOrLessMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfOneYearOrLessMember</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>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfMoreThanOneYearMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfMoreThanOneYearMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><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_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=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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<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>
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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_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</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>
</tr>
<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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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember</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>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember</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;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6822917648">
<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>Mar. 31, 2019 </div>
<div>USD ($) </div>
<div>Investment</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">353<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 727,648<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">(430)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue', window );">Estimated fair value, more than 12 months of temporary impairment</a></td>
<td class="nump">170,928<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="num">(926)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue', window );">Estimated fair value, total temporary impairment</a></td>
<td class="nump">898,576<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss', window );">Unrealized losses, total temporary impairment</a></td>
<td class="num">$ (1,356)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAbstract', 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="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">275<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 530,786<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">(306)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue', window );">Estimated fair value, more than 12 months of temporary impairment</a></td>
<td class="nump">102,815<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="num">(561)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue', window );">Estimated fair value, total temporary impairment</a></td>
<td class="nump">633,601<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss', window );">Unrealized losses, total temporary impairment</a></td>
<td class="num">$ (867)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAbstract', 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="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">24<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 91,005<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">(81)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue', window );">Estimated fair value, more than 12 months of temporary impairment</a></td>
<td class="nump">16,534<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="num">(46)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue', window );">Estimated fair value, total temporary impairment</a></td>
<td class="nump">107,539<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss', window );">Unrealized losses, total temporary impairment</a></td>
<td class="num">$ (127)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAbstract', 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="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">15<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 94,603<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">(34)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue', window );">Estimated fair value, more than 12 months of temporary impairment</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue', window );">Estimated fair value, total temporary impairment</a></td>
<td class="nump">94,603<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss', window );">Unrealized losses, total temporary impairment</a></td>
<td class="num">$ (34)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAbstract', 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="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">39<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 11,254<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">(9)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue', window );">Estimated fair value, more than 12 months of temporary impairment</a></td>
<td class="nump">51,579<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="num">(319)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue', window );">Estimated fair value, total temporary impairment</a></td>
<td class="nump">62,833<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss', window );">Unrealized losses, total temporary impairment</a></td>
<td class="num">$ (328)<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_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investments in debt and equity securities classified as available-for-sale that have been in a continuous loss position for twelve months or longer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss</td>
</tr>
<tr>
<td style="padding-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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAbstract</td>
</tr>
<tr>
<td style="padding-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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investments in debt and equity securities classified as available-for-sale in a continuous loss position.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=82897076&amp;loc=d3e27337-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss</td>
</tr>
<tr>
<td style="padding-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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>This item represents the aggregate fair value of investments in debt and equity securities in an unrealized loss position which are categorized neither as held-to-maturity nor trading securities.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue</td>
</tr>
<tr>
<td style="padding-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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investments in debt and equity securities classified as available-for-sale that have been in a continuous loss position for less than twelve months.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss</td>
</tr>
<tr>
<td style="padding-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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>This item represents the aggregate fair value of investments in debt and equity securities categorized neither as held-to-maturity nor trading securities that have been in a continuous unrealized loss position for less than twelve months.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue</td>
</tr>
<tr>
<td style="padding-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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>This item represents the aggregate fair value of investments in debt and equity securities categorized neither as held-to-maturity nor trading securities that have been in a continuous unrealized loss position for twelve months or longer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue</td>
</tr>
<tr>
<td style="padding-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_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of investment positions in available-for-sale investments in a continuous unrealized loss position for which an other-than-temporary impairment (OTTI) has not been recognized in the income statement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (b)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=82897076&amp;loc=d3e27290-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1</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> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</td>
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<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember</td>
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6836681184">
<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>Mar. 31, 2019</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2018</div></th>
<th class="th"><div>Mar. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR Therapeutics N.V.</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 968<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 1,349<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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 Percent 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="top.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="top.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">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member', window );">Significant Other Observable Inputs (Level 2) [Member] | 1 Percent 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="top.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="top.Show.showAR( this, 'defref_us-gaap_NotesPayableFairValueDisclosure', window );">Fair value of convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 928,400<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">146,542<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 146,281<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="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR Therapeutics N.V.</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">968<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,349<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="top.Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,067,564<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2,017,298<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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,231,154<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">1,252,960<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">27,100<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">50,200<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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="nump">245,308<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">276,612<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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">361,997<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[6]</sup></td>
<td class="nump">260,154<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[7]</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="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities issued by the U.S. Treasury [Member] | Cash and Cash Equivalents [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">15,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">14,200<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="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="nump">78,663<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">79,942<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="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="nump">2,932<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">146,542<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">146,281<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="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR Therapeutics N.V.</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="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">508,539<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">406,435<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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">361,997<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">260,154<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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR Therapeutics N.V.</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="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,558,057<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,609,514<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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,231,154<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">1,252,960<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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">245,308<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">276,612<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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">78,663<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">79,942<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="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,932<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR Therapeutics N.V.</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">968<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,349<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="top.Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">968<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,349<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="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="7"></td></tr>
<tr><td colspan="7"><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 on our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Included in other current assets on our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">$27.1 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[4]</td>
<td style="vertical-align: top;" valign="top">$50.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[5]</td>
<td style="vertical-align: top;" valign="top">Included in short-term investments on our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[6]</td>
<td style="vertical-align: top;" valign="top">$15.0 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[7]</td>
<td style="vertical-align: top;" valign="top">$14.2 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=99377789&amp;loc=d3e19207-110258<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetsFairValueDisclosure</td>
</tr>
<tr>
<td style="padding-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_AvailableForSaleSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt and equity securities categorized neither as held-to-maturity nor trading.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecurities</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>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_CashAndCashEquivalentsFairValueDisclosure">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashAndCashEquivalentsFairValueDisclosure</td>
</tr>
<tr>
<td style="padding-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_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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_EquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=99377092&amp;loc=SL75136599-209740<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_FairValueNetAssetLiabilityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FairValueNetAssetLiabilityAbstract</td>
</tr>
<tr>
<td style="padding-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_NotesPayableFairValueDisclosure">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of notes payable.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19,20,22)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NotesPayableFairValueDisclosure</td>
</tr>
<tr>
<td style="padding-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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ConvertibleSeniorNotes1PercentMember</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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member</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>
</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_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember</td>
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<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=us-gaap_CorporateDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
</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_BalanceSheetLocationAxis=us-gaap_CashAndCashEquivalentsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_BalanceSheetLocationAxis=us-gaap_CashAndCashEquivalentsMember</td>
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<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>
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</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=us-gaap_USGovernmentAgenciesDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
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<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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</table></div>
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</table>
<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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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>
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<tr>
<td><strong> Period Type:</strong></td>
<td></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_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>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>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_OtherDebtSecuritiesMember</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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<tr>
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<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel1Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel1Member</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>
</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel3Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>50
<FILENAME>R40.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6834209008">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Operating Leases (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2019 </div>
<div>USD ($) </div>
<div>Option</div>
</th>
<th class="th">
<div>Mar. 31, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [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="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAsset', window );">Right-of-use operating lease assets</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 13,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Operating lease liabilties</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">$ 17,960<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="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1', window );">Weighted average remaining lease term</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">9 years<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="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent', window );">Weighted average discount rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">7.60%<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="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrent', window );">Current portion of operating lease liabilties</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 2,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeasePayments', window );">Operating lease cash payments</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,000<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="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract', window );"><strong>Annual Future Minimum Payments Under Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths', window );">Remainder of 2019</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,341<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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo', window );">2020</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3,008<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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree', window );">2021</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,725<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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour', window );">2022</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,539<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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive', window );">2023</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,505<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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive', window );">Thereafter</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">11,862<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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Total minimum payments</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">24,980<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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount', window );">Imputed interest</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(7,020)<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="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Total lease liabilities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">17,960<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="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseExpense', window );">Rent expense</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 900<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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember', window );">Office and Laboratory Space Adjacent to Manufacturing Facility [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="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2<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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember', window );">Office Space Subleased to Akcea [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="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1<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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | Office Space for Corporate Headquarters [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="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Term of lease</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">123 months<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="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeasePeriodOfFreeRent', window );">Period of free rent under lease</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">3 months<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="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeaseAllowanceForTenantImprovements', window );">Tenant improvement allowance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 3,800<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="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation', window );">Initial amount of letter of credit</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,400<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="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate', window );">Letter of credit on third anniversary of rent commencement date</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,800<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="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate', window );">Letter of credit on fifth anniversary of rent commencement date</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="4"></td></tr>
<tr><td colspan="4"><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 deposits and other assets on our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Current portion of $2.0 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.</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_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of options to extend the lease under the lessee's operating leasing arrangement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseAllowanceForTenantImprovements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Allowance for tenant improvements to the office space included in the lessee's operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_LesseeOperatingLeaseAllowanceForTenantImprovements</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_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Initial letter of credit provided to lessor to secure lease obligation under lessee's operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation</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_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the fifth anniversary of the rent commencement date.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate</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_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the third anniversary of the rent commencement date.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate</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_LesseeOperatingLeasePeriodOfFreeRent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Period of time in which the rent is free under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_LesseeOperatingLeasePeriodOfFreeRent</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_LesseeDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue</td>
</tr>
<tr>
<td style="padding-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_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due after fifth fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive</td>
</tr>
<tr>
<td style="padding-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_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due in next fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths</td>
</tr>
<tr>
<td style="padding-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_LesseeOperatingLeaseLiabilityPaymentsDueYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due in fifth fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive</td>
</tr>
<tr>
<td style="padding-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_LesseeOperatingLeaseLiabilityPaymentsDueYearFour">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due in fourth fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour</td>
</tr>
<tr>
<td style="padding-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_LesseeOperatingLeaseLiabilityPaymentsDueYearThree">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due in third fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree</td>
</tr>
<tr>
<td style="padding-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_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due in second fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo</td>
</tr>
<tr>
<td style="padding-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_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments in excess of discounted obligation for lease payments for operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount</td>
</tr>
<tr>
<td style="padding-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_LesseeOperatingLeaseRenewalTerm">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease renewal, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918673-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseRenewalTerm</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseTermOfContract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918673-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseTermOfContract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<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_OperatingLeaseExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of operating lease expense. Excludes sublease income.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 4<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918638-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseExpense</td>
</tr>
<tr>
<td style="padding-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_OperatingLeaseLiabilitiesPaymentsDueAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract</td>
</tr>
<tr>
<td style="padding-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_OperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiability</td>
</tr>
<tr>
<td style="padding-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_OperatingLeaseLiabilityCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease, classified as current.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityCurrent</td>
</tr>
<tr>
<td style="padding-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_OperatingLeasePayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow from operating lease, excluding payments to bring another asset to condition and location necessary for its intended use.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 5<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918643-209977<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeasePayments</td>
</tr>
<tr>
<td style="padding-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_OperatingLeaseRightOfUseAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_OperatingLeaseWeightedAverageDiscountRatePercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Weighted average discount rate for operating lease calculated at point in time.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(4)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918686-209980<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI http://asc.fasb.org/extlink&amp;oid=77888399&amp;loc=SL77918982-209971<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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_OperatingLeaseWeightedAverageRemainingLeaseTerm1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Weighted average remaining lease term for operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI http://asc.fasb.org/extlink&amp;oid=77888399&amp;loc=SL77918982-209971<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember</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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember</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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceForCorporateHeadquartersMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceForCorporateHeadquartersMember</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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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6661178672">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2019 </div>
<div>USD ($) </div>
<div>Component</div>
</th>
<th class="th">
<div>Mar. 31, 2018 </div>
<div>USD ($)</div>
</th>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract', window );"><strong>Income Taxes [Abstract]</strong></a></td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateContinuingOperations', window );">Effective tax rate</a></td>
<td class="nump">25.50%<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="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate', window );">Federal statutory rate</a></td>
<td class="nump">21.00%<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="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Income tax expense | $</a></td>
<td class="nump">$ 31,047<span></span>
</td>
<td class="nump">$ 15<span></span>
</td>
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<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfIncomeTaxExpenseComponents', window );">Number of income tax expense components | Component</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<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_ions_NumberOfIncomeTaxExpenseComponents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of income tax expense components.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_NumberOfIncomeTaxExpenseComponents</td>
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<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:integerItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<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_EffectiveIncomeTaxRateContinuingOperations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Percentage of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08.(h)(2))<br> -URI http://asc.fasb.org/extlink&amp;oid=26873400&amp;loc=d3e23780-122690<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 13<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32698-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateContinuingOperations</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>num:percentItemType</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></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
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<tr>
<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_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Percentage of domestic federal statutory tax rate applicable to pretax income (loss).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I)<br> -URI http://asc.fasb.org/extlink&amp;oid=34349781&amp;loc=d3e330036-122817<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 13<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32698-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate</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>
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<tr>
<td><strong> Balance 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_IncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=26873400&amp;loc=d3e23780-122690<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109238882&amp;loc=d3e38679-109324<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6822966144">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Biogen (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="3">3 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Apr. 30, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2019 </div>
<div>USD ($) </div>
<div>Drug</div>
</th>
<th class="th">
<div>Jun. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 297,214<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 144,419<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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">59,711<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">41,081<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="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D [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="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 229,126<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">102,396<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', 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="top.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="top.Show.showAR( this, 'defref_ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases', window );">Number of additional drugs in clinical development to treat neurodegenerative diseases | Drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,100,000<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">84,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 51,900<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="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 556,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 580,900<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', 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="top.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="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">28.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">36.00%<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 59,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 41,100<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member] | R&amp;D [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="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 24,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,800<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember', window );">2018 Strategic Neurology [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="top.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="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceivedIncludingPurchaseOfStock', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,000,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember', window );">2018 Strategic Neurology [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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_MilestonePaymentsReceived', window );">Milestone payment received</a></td>
<td class="nump">$ 7,500<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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialMilestonePayment', window );">Next prospective milestone</a></td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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<tr>
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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 class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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<td>ions_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of milestone payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_MilestonePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td>duration</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPotentialMilestonePayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The next potential milestone payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialMilestonePayment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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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>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of additional drugs in clinical development to treat neurodegenerative diseases under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases</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>
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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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</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceivedIncludingPurchaseOfStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The total amount of the upfront payment received, including the purchase of shares of the Company's stock, under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_UpfrontPaymentReceivedIncludingPurchaseOfStock</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>
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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=109250915&amp;loc=d3e13531-108611<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109250915&amp;loc=d3e13537-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130531-203044<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130532-203044<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130543-203045<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130539-203045<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130545-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_SPINRAZARoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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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_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</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>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementsAndLicensingAgreementsBiogenMember</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>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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=ions_RevenueFromContractWithCustomerBenchmarkMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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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<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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</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>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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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<td>na</td>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6823164976">
<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="1">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2019 </div>
<div>USD ($) </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Mar. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 297,214<span></span>
</td>
<td class="nump">$ 144,419<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="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 229,126<span></span>
</td>
<td class="nump">$ 102,396<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember', 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | Agreement</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="nump">$ 67,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 72,600<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember', 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">14.00%<span></span>
</td>
<td class="nump">1.00%<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember', window );">Roche [Member] | R&amp;D [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 41,200<span></span>
</td>
<td class="nump">$ 2,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember', window );">Huntington's Disease [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | Agreement</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 220,000<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="top.Show.showAR( this, 'defref_ions_NextPotentialMilestonePayment', window );">Next prospective milestone</a></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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember', window );">Huntington's Disease [Member] | IONIS-HTT [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 35,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember', 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | Agreement</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_NextPotentialMilestonePayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The next potential milestone payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialMilestonePayment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfCollaborationAgreements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of collaboration agreements with the collaboration partner.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=109250915&amp;loc=d3e13531-108611<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109250915&amp;loc=d3e13537-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130531-203044<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130532-203044<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130543-203045<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130539-203045<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130545-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementsAndLicensingAgreementsRocheMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=ions_RevenueFromContractWithCustomerBenchmarkMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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=ions_RevenueFromContractWithCustomerBenchmarkMember</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember</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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<td><strong> Period Type:</strong></td>
<td></td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_HttMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_HttMember</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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<tr>
<td><strong> Data Type:</strong></td>
<td>na</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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember</td>
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<tr>
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<tr>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6835860448">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Novartis (Details) - USD ($)<br> $ in Thousands, shares in Millions</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2018</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 297,214<span></span>
</td>
<td class="nump">$ 144,419<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="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">229,126<span></span>
</td>
<td class="nump">$ 102,396<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="nump">$ 23,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 28,800<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">53.00%<span></span>
</td>
<td class="nump">12.00%<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 330,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | AKCEA-APO(a)-L [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">150,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | R&amp;D [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">157,100<span></span>
</td>
<td class="nump">$ 17,100<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="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_SublicenseFeePaidForLicenseOfDrug', window );">Sublicense fee paid in stock</a></td>
<td class="nump">$ 75,000<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="top.Show.showAR( this, 'defref_ions_ReceiptOfSharesInSubsidiary', window );">Additional shares of Akcea stock received (in shares)</a></td>
<td class="nump">2.8<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_ReceiptOfSharesInSubsidiary">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of shares received from the subsidiary during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_ReceiptOfSharesInSubsidiary</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_SublicenseFeePaidForLicenseOfDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of the sublicense fee paid in common stock.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_SublicenseFeePaidForLicenseOfDrug</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_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=109250915&amp;loc=d3e13531-108611<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109250915&amp;loc=d3e13537-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130531-203044<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=82913815&amp;loc=SL49130532-203044<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130543-203045<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130539-203045<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=109196051&amp;loc=SL49130545-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</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=ions_RevenueFromContractWithCustomerBenchmarkMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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=ions_RevenueFromContractWithCustomerBenchmarkMember</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td style="white-space:nowrap;">srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</td>
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<DOCUMENT>
<TYPE>XML
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<head>
<title></title>
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<span style="display: none;">v3.19.1</span><table class="report" border="0" cellspacing="2" id="idp6837161264">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Segment Information (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2019 </div>
<div>USD ($) </div>
<div>Segment</div>
</th>
<th class="th">
<div>Mar. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th"><div>Apr. 30, 2018</div></th>
<th class="th"><div>Jul. 31, 2017</div></th>
<th class="th"><div>Jun. 30, 2017</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_NumberOfReportableSegments', window );">Number of reportable segments | Segment</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 297,214<span></span>
</td>
<td class="nump">$ 144,419<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">175,679<span></span>
</td>
<td class="nump">147,720<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="nump">121,535<span></span>
</td>
<td class="num">(3,301)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets as of current period</a></td>
<td class="nump">2,835,889<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,667,784<span></span>
</td>
<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="top.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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">68,088<span></span>
</td>
<td class="nump">42,023<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="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">59,711<span></span>
</td>
<td class="nump">41,081<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=us-gaap_ProductMember', window );">TEGSEDI Product Sales, 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">6,754<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember', window );">Licensing and Other 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">1,623<span></span>
</td>
<td class="nump">942<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue Under Collaborative Agreements [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="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 229,126<span></span>
</td>
<td class="nump">102,396<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [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="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="nump">76.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [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="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 221,890<span></span>
</td>
<td class="nump">132,540<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">114,515<span></span>
</td>
<td class="nump">105,544<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="nump">107,375<span></span>
</td>
<td class="nump">26,996<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets as of current period</a></td>
<td class="nump">3,112,235<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,975,491<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">61,334<span></span>
</td>
<td class="nump">42,023<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="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">59,711<span></span>
</td>
<td class="nump">41,081<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | TEGSEDI Product Sales, 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | Licensing and Other 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">1,623<span></span>
</td>
<td class="nump">942<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | R&amp;D Revenue Under Collaborative Agreements [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="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">160,556<span></span>
</td>
<td class="nump">90,517<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [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="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">163,816<span></span>
</td>
<td class="nump">17,108<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">137,610<span></span>
</td>
<td class="nump">47,435<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="nump">26,206<span></span>
</td>
<td class="num">(30,327)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets as of current period</a></td>
<td class="nump">458,717<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">365,261<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">6,754<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | TEGSEDI Product Sales, 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">6,754<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | Licensing and Other 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | R&amp;D Revenue Under Collaborative Agreements [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="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">157,062<span></span>
</td>
<td class="nump">17,108<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [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="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="num">(88,492)<span></span>
</td>
<td class="num">(5,229)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="num">(76,446)<span></span>
</td>
<td class="num">(5,259)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="num">(12,046)<span></span>
</td>
<td class="nump">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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets as of current period</a></td>
<td class="num">(735,063)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (672,968)<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | TEGSEDI Product Sales, 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | Licensing and Other 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | R&amp;D Revenue Under Collaborative Agreements [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="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="num">$ (88,492)<span></span>
</td>
<td class="num">$ (5,229)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Assets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all assets that are recognized. Assets are probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(11))<br> -URI http://asc.fasb.org/extlink&amp;oid=6876686&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(12))<br> -URI http://asc.fasb.org/extlink&amp;oid=6879938&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_CostsAndExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -URI http://asc.fasb.org/extlink&amp;oid=115205541&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</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_MinorityInterestOwnershipPercentageByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestOwnershipPercentageByParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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_NumberOfReportableSegments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of segments reported by the entity. A reportable segment is a component of an entity for which there is an accounting requirement to report separate financial information on that component in the entity's financial statements.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NumberOfReportableSegments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The net result for the period of deducting operating expenses from operating revenues.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
